Gina Mauro

phase 2 DESTINY-Gastric01 trial (NCT03329690), treatment with 

am-trastuzumab deruxtecan-nxki (Enhertu) acheived a 40% reduction in the risk of death compared with standard chemotherapy in patients with HER2-positive gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma, according to updated survival results o presented during the 2022 Gastrointestinal Cancers Symposium.

The updated median overall survival (OS) with trastuzumab deruxtecan remained at 12.5 months (95% CI, 10.3-15.2) compared with 8.9 months (95% CI, 6.4-10.4) with chemotherapy (HR, 0.60; 95% CI, 0.42-0.86).

“With continued follow-up after the primary analysis, trastuzumab deruxtecan demonstrated a clinically meaningful OS benefit and clinically relevant improvement in [objective response rate] compared with standard chemotherapy in HER2-positive advanced gastric or GEJ cancer,” lead study author Kensei Yamaguchi, of The Cancer Institute Hospital of the Japanese Foundation for Cancer Research in Tokyo, Japan, said in a presentation during the meeting.

In January 2021, the FDA approved trastuzumab deruxtecan for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma who have received a previous trastuzumab (Herceptin)-based regimen.

The regulatory decision was based on primary findings from the phase 2 DESTINY-Gastric01 study, which showed that the median OS with trastuzumab deruxtecan was 12.5 months (95% CI, 9.6-14.3) compared with 8.4 months (95% CI, 6.9-10.7) with irinotecan or paclitaxel in patients with advanced, HER2-positive gastric or GEJ adenocarcinoma who had progressed following a trastuzumab-based treatment (HR, 0.59; 95% CI, 0.39-0.88; 

DESTINY-Gastric01 is an open-label, multicenter, randomized, phase 2 study. Investigators evaluated trastuzumab deruxtecan versus physician’s choice of standard chemotherapy in patients with HER2-expressing advanced gastric or GEJ adenocarcinoma who had received at least 2 prior regimens, including fluoropyrimidine, a platinum-based agent, and trastuzumab or approved biosimilar.

Patients who had or were suspected to have interstitial lung disease (ILD) or pneumonitis, or a history of noninfectious ILD or pneumonitis that had been treated with steroids, were excluded from enrollment.

A total 188 patients were randomized 2:1 to receive either trastuzumab deruxtecan at 6.4 mg/kg every 3 weeks (n = 126) or chemotherapy with irinotecan or paclitaxel (n = 62). Eighty-six percent of participants received a prior taxane, 71% had ramucirumab (Cyramza), and 31% received prior PD-1/PD-L1 inhibitors.

Stratification factors included by country, ECOG performance status, and HER2 status.

The primary end point of the trial was objective response rate (ORR) per independent central review (ICR), while secondary end points comprised OS, duration of response (DOR), progression-free survival, confirmed ORR, and safety.

The data cutoff date for OS was June 3, 2020, after a median follow-up of 18.5 months.

The median age was 65.5 years (range, 28.0-82.0), 24.1% of patients were female, and most patients were from Japan (79.9%). Forty-nine percent of patients had an ECOG performance of 0, and patients either had intestinal histology (66.3%), diffuse (25.7%), or other (8.1%). Three-fourths of patients (76.3%) had HER2 expression and 87.6% had gastric/GEJ as their primary site. Patients had tumors measuring at less than 5 cm (46.2%), between 5 and 10 cm (31.8%), at least 10 cm (14.9%), or missing (12.1%).

Patients had received either 2 (57.1%), 3 (28.1%), or at least 4 (14.9%) prior systemic therapies, which consisted of trastuzumab (100%), ramucirumab (70.7%), taxane (86.4%), irinotecan or another topoisomerase I inhibitor (7.3%), or an immune checkpoint inhibitor (31.3%). Patients in the trastuzumab deruxtecan group were more than twice as likely to have received 4 or more prior therapies (20.0% vs 9.7%).

Additional data with the longer follow-up showed that the ORR by ICR was 51.3% (95% CI, 41.9%-60.5%) and 14.3% (95% CI, 6.4%-26.2%) with trastuzumab deruxtecan and chemotherapy, respectively, which Yamaguchi said was a statistically significant difference. In the trastuzumab deruxtecan arm, this consisted of a 9.2% complete response (CR) rate and a 42.0% partial response (PR) rate; the stable disease (SD) rate was 35.3% and the progressive disease (PD) rate was 11.8%. Two patients (1.7%) were not evaluable for response.

The confirmed ORR was 42.0% (95% CI, 33.0%-51.4%) with trastuzumab deruxtecan and 12.5% (95% CI, 5.2%-24.1%) with chemotherapy. In the trastuzumab deruxtecan arm, the CR and PR rates were 8.4% and 33.6%, respectively; the SD and PD rates were 43.7% and 11.8%, respectively. Three patients (2.5%) were not evaluable for response.

The confirmed disease control rate was 85.7% (95% CI, 78.1%-91.5%) with trastuzumab deruxtecan compared with 62.5% (95% CI, 48.5%-75.1%) with chemotherapy. The confirmed median DOR was 12.5 months (95% CI, 5.6–not evaluable) and 3.9 months (95% CI, 3.0-4.9), respectively. The median time to response was similar between arms, at 1.5 months (95% CI, 1.4-1.7) with trastuzumab deruxtecan and 1.6 months (95% CI, 1.3-1.7) with chemotherapy.

“This presentation shows that most patients received [trastuzumab deruxtecan had a reduction in tumor size compared with approximately half of patients receiving [chemotherapy],” Yamaguchi said.

Regarding safety, grade 3 or higher adverse events (AEs) occurred in 85.6% of patients on trastuzumab deruxtecan compared with 56.5% of those on chemotherapy. The most common grade or higher AE was decreased neutrophil count (51.2% with trastuzumab deruxtecan vs 24.2% with chemotherapy), followed by anemia (38.4% vs 22.6%, respectively) and decreased white blood cell count (20.8% vs 11.3%).

Sixteen patients (12.8%) experienced ILD/pneumonitis related to trastuzumab deruxtecan as determined by an independent adjudication committee. These occurred at levels of grade 1/2 (n = 13), grade 3 (n = 2), and grade 4 (n = 1). Four ILD/pneumonitis events occurred since the primary analysis; 1 was a grade 1 event and the remaining 3 were grade 2.

The median time to first onset among the 16 overall ILD/pneumonitis events was 102.5 days (range, 36-638).

One treatment-related death from pneumonia occurred on the trastuzumab deruxtecan arm, which had been reported in the primary analysis. No ILD/pneumonitis events nor AE-related deaths occurred on the chemotherapy arm.

“This additional follow-up provides further evidence that trastuzumab deruxtecan is an effective treatment option for patients with HER2-positive advanced gastric cancer or GEJ adenocarcinoma who have progressed after 2 or more previous lines of therapy, including trastuzumab, fluoropyrimidine, and a platinum agent,” Yamaguchi concluded.

DESTINY-Gastric01 trial also has 2 exploratory cohorts focused on the HER2-low population: HER2 (immunohistochemistry [IHC] 2+/in situ hybridization —; n = 21) and HER2 (IHC 1+; n = 24).

1. Yamaguchi K, Bang Y-J, Iwasa S, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2–positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: Final overall survival (OS) results from a randomized, multicenter, open-label, phase 2 study (DESTINY-Gastric01). 

. 2022;40(suppl;242). doi:10.1200/JCO.2022.40.4_suppl.242

2. FDA approves fam-trastuzumab deruxtecan-nxki for HER2-positive gastric adenocarcinomas. News release. FDA. January 15, 2021. Accessed January 15, 2021. http://bit.ly/35KBZ8T.

3. Shitara K, Bang Y-J, Iwasa S, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: a randomized, phase II, multicenter, open-label study (DESTINY-Gastric01). 

. 2020;38(suppl 15):4513). doi:10.1200/JCO.2020.38.15_suppl.4513

Articles

Updated survival results from the phase 2 DESTINY-Gastric01 trial reveal the survival benefit of trastuzumab deruxtecan HER2-positive gastric cancer or gastroesophageal junction adenocarcinoma.

Trastuzumab Deruxtecan Extends Overall Survival in HER2+ Advanced Gastric/GEJ Cancer

Treatment options for endometrial cancer have evolved over recent years, with significant progress seen in 2021 for treating the distinct molecularly-driven subtypes of endometrial cancer. In a presentation during the 39th Annual Chemotherapy Foundation Symposium (CFS®), Bhavana Pothuri, MD, MS, explained the recent advances in subtypes and treatment options for patients with endometrial cancer.

Moreover, Pothuri added that phase 3 trials of other immune-based combinations with chemotherapy, PARP inhibitors, and other novel agents are on the horizon for 2022 and beyond to target some of these select subsets.

“The endometrial cancer treatment paradigm has changed significantly and will continue to evolve,” said Pothuri, a professor in the Department of Obstetrics and Gynecology and Medicine at NYU Grossman School of Medicine, and director of Gynecologic Oncology Clinical Trials at NYU Langone Health’s Laura & Isaac Perlmutter Cancer Center.

Endometrial cancer is comprised of 4 distinct subtypes: POLE-mutant, microsatellite instability– high (MSI-H)/mismatch repair deficient (dMMR), copy number (CN) low, and CN high/

abnormal. Patients with POLE-mutant disease tend to have the best prognosis compared with CN-low and MSI/dMMR disease (intermediate outcomes), and CN-high/TP53 abnormal disease (worst prognosis).

Up until 2017, the sole FDA-approved therapy in the endometrial cancer armamentarium was megestrol acetate. Now, clinical practice has benefitted from 3 new regimens that are available based on patients’ molecular profiles: dostarlimab-gxly (Jemperli), pembrolizumab (Keytruda), and pembrolizumab plus lenvatinib (Lenvima).

Recent Regulatory Advances in Endometrial Cancer Treatment 

The multicenter, single-arm, multiple parallel-cohort, open-label, phase 1b GARNET trial (NCT02715284) evaluated single-agent dostarlimab, a PD-1 inhibitor, in expansion cohorts across multiple tumor types, including endometrial cancer. Patients were treated with dostarlimab at 500 mg of intravenous (IV) every 3 weeks for 4 cycles followed by 1000 mg IV every 6 weeks until disease progression.

The trial featured dose-finding (part 1), fixed-dose safety run-in (part 2A), and expansion cohorts (part 2B). In the expansion cohort, there were 5 groups: dMMR endometrial cancer, MMR proficient (pMMR) endometrial cancer, non–small cell lung cancer, nonendometrial dMMR/MSI-H cancer, and platinum-resistant ovarian cancer.

Dostarlimab elicited a 42.3% ORR in 71 patients with dMMR recurrent or advanced endometrial cancer, which included a 12.7% CR rate and a 29.6% PR rate.

 The DOR was at least 6 months for 93.3% of responders, and the median DOR was NR at a median follow-up of 14.1 months (range, 2.6-22.4+).

At a median follow-up of 16.5 months, the ORR via investigator-assessed irRECIST criteria was 45.5% in patients with dMMR endometrial cancer (n = 110).

Based on the GARNET findings, the FDA granted an accelerated approval in April 2021 to dostarlimab for the treatment of patients with recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing chemotherapy and whose cancers are dMMR, as determined by an FDA-approved test.

The safety profile with dostarlimab was also found to be manageable. Any-grade treatment-emergent AEs (TEAEs) occurred in 69.9% of patients; grade 3 or higher irTRAEs had an incidence of 1.6% or lower. Additionally, increased alanine aminotransferase led to discontinuation in 1.4% of patients, but no TRAEs led to death.

The PD-1 inhibitor pembrolizumab was explored in the open-label, nonrandomized, phase 2 KEYNOTE-158 trial (NCT02628067), which comprised previously treated patients with advanced MSI-H/dMMR tumors, including endometrial cancer. Patients received either pembrolizumab at 200 mg every 3 weeks, or at 10 mg/kg every 2 weeks.

Preliminary findings from all-comers showed that the objective response rate (ORR) was 39.6% (95% CI, 31.7%-47.9%), and responses lasting at least 6 months occurred in 78% of responders.

The FDA granted a tissue-agnostic approval in May 2017 to pembrolizumab based on the preliminary KEYNOTE-158 data, making it the first regulatory approval based on a biomarker regardless of tumor type. 

Longer follow-up of the endometrial cancer cohort was presented at the 2021 European Society of Medical Oncology Congress, which had a data cutoff date of October 5, 2020.

 In the efficacy-evaluable population of the endometrial group (cohorts D and K; n = 79), the ORR was 48% (95% CI, 37%-60%), which included a 14% complete response (CR) rate and a 34% partial response rate; 18% of patients had stable disease.

The median time to response was 2.3 months (range, 1.3-10.6). Additionally, the median duration of response (DOR) had not been reached, but 68% of patients were still in response at 3 years. The median progression-free survival (PFS) and overall survival (OS) was 13.1 months (95% CI, 4.3-34.4) and not reached (NR; 95% CI, 27.2-NR), respectively.

Safety with pembrolizumab was consistent with that of other checkpoint inhibitors. Treatment-related adverse events (TRAEs) occurring in at least 10% of patients included pruritus (24%), fatigue (21%), diarrhea (16%), arthralgia (14%), and nausea (14%), hypothyroidism (13%), and rash (11%). Immune-related AEs (irAEs) at any grade occurred in 28% of patients, but 7% of patients experienced these as grade 3/4 events, including colitis (n = 1), severe skin reactions (n = 2), type 1 diabetes mellitus (n = 1), hepatitis (n = 1), and adrenal insuffi ciency (n = 1). 

Microsatellite Stable/pMMR: Pembrolizumab/Lenvatinib The combination of pembrolizumab and lenvatinib was tested in patients with advanced endometrial cancer who received prior platinum-based chemotherapy in the phase 3 Study-309/ KEYNOTE-775 trial (NCT03517449).

At a median follow-up of 11.4 months and in those with microsatellite stable (MSS)/pMMR disease, the median OS was 17.4 months (95% CI, 14.2-19.9) with pembrolizumab/lenvatinib vs 12.0 months (95% CI, 10.8-13.3) with physician’s choice of chemotherapy (HR, 0.68; 95% CI, 0.56-0.84; 

Results showed that the median PFS in patients with pMMR status was 6.6 months (95% CI, 5.6-7.4) and 3.8 months (95% CI, 3.6-5.0) with pembrolizumab/lenvatinib and chemotherapy, respectively (HR, 0.60; 95% CI, 0.50-0.72;

 < .0001). Here, the ORR was 30.3% (95% CI, 25.5%-35.5%) with pembrolizumab/ lenvatinib vs 15.1% (95% CI, 11.5%-19.3%) with physician’s choice; the median DOR was 9.2 months (range, 1.6-23.7) vs 5.7 months (range, 0.0-24.2), respectively (

In all-comers, the median OS was 18.3 months (95% CI, 15.2-20.5) and 11.4 months (95% CI, 10.5-12,9), respectively (HR, 0.62; 95% CI, 0.51-0.75; 

 < .0001). The median PFS was 7.2 months (95% CI, 5.7-7.6) with pembrolizumab/lenvatinib and 3.8 months (95% CI, 3.6-4.2) with chemotherapy (HR, 0.56; 95% CI, 0.47-0.66; 

 < .0001). The ORRs were 31.9% (95% CI, 27.4%-36.6%) and 14.7% (95% CI, 11.4%-18.4%) with pembrolizumab/lenvatinib and physician’s choice, respectively. Finally, the median DOR was 14.4 months (range, 1.6-24.2) and 5.7 months (range, 0.0-24.2).

Results of a subgroup analysis from KEYNOTE-775 demonstrated the improvement of pembrolizumab/lenvatinib over physician’s choice of therapy in patients with dMMR endometrial cancer. The median OS with pembrolizumab/lenvatinib-treated patients was NR (95% CI, NR-NR) compared with 8.6 months (95% CI, 5.5-12.9) for physician’s choice of therapy (HR, 0.37; 95% CI, 0.22-0.62; 

Here, the median PFS was 10.7 months (95% CI, 5.6-NR) and 3.7 months (95% CI, 3.1-4.4), respectively (HR, 0.36; 95% CI, 0.23- 0.57; 

 < .0001). The ORRs were 40.0% (95% CI, 28.0%-52.9%) and 12.3% (95% CI, 5.5%- 22.8%), respectively.

The combination was given accelerated approval in September 2019, followed by a regular approval in July 2021, for use in patients with advanced endometrial carcinoma that is not MSI-H/dMMR, who have disease progression following prior systemic therapy in any setting and are ineligible for curative surgery or radiation.

Regarding safety, toxicities associated with pembrolizumab/lenvatinib were consistent with those observed with each therapy given individually. The most frequent all-grade and grade 3 or higher TEAEs included hypertension (64% and 38%, respectively), hypothyroidism (all-grade, 57%), diarrhea (54% and 8%, respectively), nausea (all-grade, 50%), and decreased appetite (45% and 8%, respectively.

Additional grade 3 or higher TEAEs with the combination included weight decrease (10%), anemia (6%), asthenia (6%), fatigue (5%), and proteinuria (5%). It should be noted that 5.7% of patients on pembrolizumab/ lenvatinib died due to grade 5 gastrointestinal disorders (1.2%), cardiac disorders (0.5%), general disorders (1.5%), infections (0.7%), decreased appetite (0.2%), and neoplasms, nervous system, psychiatric, renal, reproductive, or respiratory disorders (0.2% each). This was compared with 4.9% of patients on the physician’s choice arm.

“There are overlapping toxicities to also keep in mind, with the diarrhea and the hypothyroidism. It’s important to sort out: Are those related to the immunotherapy or to the lenvatinib?” Pothuri asked.

Ongoing phase 3 trials are tackling more checkpoint inhibitors alone or in combination in endometrial cancer, including RUBY (NCT03981796) with dostarlimab with carboplatin/paclitaxel, RUBY Part 2 with dostarlimab plus niraparib (Zejula; NCT03981796), AtTEnd (NCT03603184) with atezolizumab (Tecentriq), NRGY018 (NCT03914612) with pembrolizumab plus carboplatin/paclitaxel, KEYNOTE-B21 (NCT04634877) with pembrolizumab plus adjuvant chemotherapy with or without radiotherapy, and LEAP-001 (NCT03884101) with pembrolizumab plus lenvatinib.

Although CN-low endometrial cancer represents a subgroup of patients that has long been treated with chemotherapy, Pothuri admits that this likely not the optimal approach for this subset, which current research is attempting to confirm.

An additional trial of interest is the phase 2 ENGOT-EN3/NSGO-PALEO study (NCT02730429), which enrolled patients with primary stage IV or relapsed measurable/ evaluable endometrial cancer who have received at least 1 prior systemic therapy. Patients were randomized 1:1 to receive palbociclib (Ibrance) at 125 mg days 1 to 21 plus letrozole at 2.5 mg on days 1 to 28 vs placebo and letrozole at the same dosage schedule every 28 days until disease progression. The primary end point was investigator-assessed PFS. 

Data showed that the median PFS was 8.3 months and 3.0 months for the palbociclib/ letrozole and placebo/letrozole arms, respectively (HR, 0.56; 95% CI, 0.32-0.98; 

 = .0376).8 Additionally, the disease control rate was 63.6% and 37.8%, respectively.

“This was a phase 2 study and needs further study to determine if there is a role of CDK4/6 and hormonal therapy,” Pothuri added.

Patients with CN-high endometrial cancer form a group that is classically comprised of 

 positive-tumors, Pothuri explained, adding that homologous recombination deficiency is frequent in this subset and may be actionable.

For example, in a phase 2 trial (NCT01367002), patients with HER2-neu uterine serous carcinoma were randomized to receive carboplatin/paclitaxel for 6 cycles with or without IV trastuzumab (Herceptin) until progression or unacceptable toxicity. Data showed that in all patients the median PFS was 12.6 months with the addition of trastuzumab vs 8.0 months for carboplatin/ paclitaxel alone (HR, 0.44; 90% CI, 0.26-0.76; 

 In those with primary stage III to IV disease, the median PFS was 17.9 months and 9.3 months, respectively (HR, 0.40; 90% CI, 0.20-0.80; one-sided 

 = .013). In recurrent disease, the median PFS was 9.2 months and 6.0 months, respectively (HR, 0.14; 90% CI, 0.04-0.53; 

An updated analysis showed an OS benefit in the stage III to IV subgroup, in which the median OS was NR in the trastuzumab arm vs 25.4 months with chemotherapy alone (HR, 0.49; 90% CI, 0.25-0.97; 

“[There is] lots of great interest, and it is really an exciting time to be in the endometrial cancer space,” Pothuri said. “The role of trastuzumab and other HER2/neu-directed therapies for CN-high biomarker-positive tumors also needs further investigation in phase 3 trials.”

1. Pothuri B. Biomarker driven management of endometrial cancer. Presented at: 39th Annual CFS®: November 3-5, 2021; New York, NY. 

2. Levine DA,The Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. 

. 2013;497(7447):67-73. doi:10.1038/nature12113 

3. Oaknin A, Tinker AV, Gilbert L, et al. Clinical activity and safety of the anti–programmed death 1 monoclonal antibody dostarlimab for patients with recurrent or advanced mismatch repair–defi cient endometrial cancer: a nonrandomized phase 1 clinical trial. 

. 2020;6(11):1766-1772. doi:10.1001/jamaoncol.2020.4515 

4. Oaknin A, Gilbert L, Tinker AV, et al. Interim analysis of the immune-related endpoints of the mismatch repair defi cient (dMMR) and profi cient (MMRp) endometrial cancer cohorts from the GARNET study. 

. 2021;162(suppl 1):S12-S13. doi:10.1016/S0090- 8258(21)00672-7 

5. FDA grants accelerated approval to pembrolizumab for fi rst tissue/ site agnostic indication. FDA. May 23, 2017. Accessed November 4, 2021. https://bit.ly/3k62CMS 

6. O’Malley DM, Bariani GM, Cassier PA, et al. Pembrolizumab (pembro) in patients (pts) with microsatellite instability-high (MSI-H) advanced endometrial cancer (EC): Updated results from KEYNOTE-158. 

. 2021;32(suppl_5):S725-S772. doi:10.1016/annonc/ annonc703 

7. Makker V, Colombo N, Herráez AC, et al. A multicenter, open-label, randomized, phase 3 study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer: Study 309/KEYNOTE-775. 

. 2021;162(suppl 1):S4. doi:10.1016/ S0090-8258(21)00657-0

8. Mirza MR, BjørgeL, Marmé F, et al. A randomised double-blind placebo-controlled phase II trial of palbociclib combined with letrozole (L) in patients (pts) with oestrogen receptor-positive (ER+) advanced/ recurrent endometrial cancer (EC): NSGO-PALEO / ENGOT-EN3 trial. 

. 2020;31(suppl_4):S1142-S1215. doi:10.1016/annonc/ annonc325 

9. Fader AN, Roque DM, Siegel E, et al. Randomized phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. 

l. 2018;36(20):2044-2051. doi:10.1200/JCO.2017.76.5966 

10. Fader AN, Roque DM, Siegel E, et al. Randomized phase II trial of carboplatin-paclitaxel compared with carboplatin-paclitaxel-trastuzumab in advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress her2/neu (NCT01367002): updated overall survival analysis. 

. 2020;26(15):3928-3935. doi:10.1158/1078-0432.CCR-20-0953

In a presentation during the 39th Annual Chemotherapy Foundation Symposium, Bhavana Pothuri, MD, MS, explained the recent advances in subtypes and treatment options for patients with endometrial cancer.

ICIs Provide New Treatment Options for Subtypes of Endometrial Cancer 

An analysis of the MEDALIST study (NCT02631070) showed more durable response with luspatercept-aamt (Reblozyl) treatment compared with placebo in patients with lower-risk myelodysplastic syndrome (LR-MDS) and anemia that is refractory to or ineligible for erythropoiesis-stimulating agent (ESA) therapy, findings presented during the ASH Annual Meeting 2021 demonstrate.

Data showed that luspatercept also had a more tolerable safety profile when adjusted for exposure. Prior to this, there was a higher proportion of patients on luspatercept vs placebo who experienced fatigue at 30.1% vs 14.5%, respectively. Following exposure adjustment, these rates were more balanced at 26.2 vs 27.1 events per 100 patient-years, respectively.

Additionally, a small number of patients progressed to higher-risk MDS or acute myeloid leukemia (AML), the incidence of which proved to be comparable between the arms. However, those on luspatercept had a longer median time of progression to AML vs those on the placebo arm.

“Up through week 48, patients randomized to luspatercept in the MEDALIST study remained on treatment longer and had more durable and repeated episodes of red blood cell–transfusion independence [RBC-TI] response events than patients on placebo,” Uwe Platzbecker, MD, director of the medical clinic, University Hospital Leipzig, said in a virtual poster presentation on the data.

Patients with LR-MDS who are refractory or ineligible for treatment with ESAs have limited therapeutic options for anemia, Platzbecker noted. Luspatercept, a first-in-class erythroid maturation agent that enhances late-stage erythropoiesis, has FDA and European Medicines Agency indications for the treatment of patients with LR-MDS.

Specifically, the FDA approved luspatercept in April 2020 for the treatment of anemia failing an ESA and requiring 2 or more red blood cell (RBC) units over 8 weeks in adult patients with very low- to intermediate-risk MDS with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.

The regulatory decision is based on overall findings from the phase 3 MEDALIST trial, which showed that luspatercept significantly reduced transfusion burden compared with placebo in patients with LR-MDS.

In the MEDALIST analysis that was presented at the 2021 ASH Annual Meeting, investigators sought to further characterize the effects of luspatercept in this patient population, including duration of treatment and response, median number of study treatment doses received, duration of RBC-TI responses, number of responses per patient, exposure-adjusted rates of treatment-emergent adverse effects (TEAEs), and time to progression to AML.

In MEDALIST, patients had the following: MDS-RS, which comprised at least 15% ring sideroblasts or at least 5% with a 

 mutation, with less than 5% blasts in bone marrow and without del(5q); Revised International Prognostic Scoring System very low-, low-, or intermediate-risk MDS; RBC transfusion dependence (mean ≥2 units per 8 weeks). Moreover, patients must have been either refractory or intolerant to ESAs or be ESA naïve and unlikely to respond to these agents. Patients could not have received prior treatment with disease-modifying agents.

Participants were randomized 2:1 to receive luspatercept at 1.0 mg/kg subcutaneously every 21 days (n = 153) or placebo every 3 weeks (n = 76). On the luspatercept arm, doses were titrated up to a maximum of 1.75 mg/kg. Crossover between the 2 groups was not permitted.

Disease and response assessments were done at week 25 and again every 6 months. Patients were followed for at least 3 years after the final dose for AML progression, subsequent MDS treatment, and overall survival.

As of November 26, 2020, the median duration of treatment was 50.9 weeks (range, 6-207) in the luspatercept arm vs 24.0 weeks (range, 7-103) in the placebo arm; the median doses of study treatment were 17 (range, 2-66) and 8 (range, 3-34), respectively. Moreover, the highest dose level received was 1.75 mg/kg in 68.6% of luspatercept-treated patients and 84.2% in placebo-treated patients.

Duration of response (DOR) was longer with luspatercept than placebo. In patients who achieved RBC-TI for 8 weeks or longer in weeks 1 to 24, the median DOR was 30.2 weeks (range, 8.1-201.1) and 13.6 weeks (range, 9.1-66.4) in patients on luspatercept vs placebo, respectively. In those who achieved RBC-TI for 8 weeks or more in weeks 1 to 48, the median DOR was 29.9 weeks (range, 8.1-201.1) and 17.4 weeks (range, 9.1-66.4), respectively.

Investigators also evaluated the number of responses occurring in responders during the entire treatment period. In the luspatercept responders (n = 58), patients either had 1 (20.7%), 2 (29.3%), 3 (22.4%), or 4 or more responses (27.6%). In the placebo responders (n = 10), 6 patients had 1 response (60.0%), 3 had 2 responses (30.0%), and 1 had 3 responses (10.0%).

“Most responding patients in the luspatercept group had multiple, separate responses,” Platzbecker said.

Regarding safety, luspatercept was still found to have a tolerable safety profile after adjusting for exposure. Exposure-adjusted TEAE incidence rates per 100 person-years included: dizziness (19.2% with luspatercept vs 8.9% with placebo), bronchitis (10.7% vs 2.2%, respectively), diarrhea (25.8% vs 18.4%), nausea (20.1% vs 13.7%), fatigue (26.2% vs 27.1%), asthenia (22.3% vs 21.5%), nasopharyngitis (8.8% vs 9.0%), cough (19.8% vs 25.0%), anemia (8.2% vs 13.6%), and arthralgia (6.3% vs 21.1%).

When investigating the median time from initial MDS diagnosis to AML progression, which occurred in 2.6% of luspatercept-treated patients and 3.9% of those on placebo, Platzbecker noted that this was 61.7 months (range, 56.7-223.6) with luspatercept and 32.7 months (range, 30.1-60.4) with placebo.

In December 2021, the FDA granted priority review to a supplemental biologics license application for luspatercept for the treatment of anemia in adults with non–transfusion dependent β-thalassemia. The European Medicines Agency has also validated the Type II variation for the agent’s use in the same indication.

1. Platzbecker U, Santini V, Komrokji RS, et al. Analysis of duration of response, exposure-adjusted safety, and progression to acute myeloid leukemia for patients with lower-risk myelodysplastic syndromes receiving luspatercept in the MEDALIST study. Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 1524.

2. US Food and Drug Administration (FDA) approves Reblozyl (luspatercept-aamt), the first and only erythroid maturation agent, to treat anemia in adults with lower-risk myelodysplastic syndromes (MDS). New release. Bristol Myers Squibb; April 3, 2020. Accessed December 12, 2021. 

3. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. 

 2020;382(2):140–151). doi:10.1056/NEJMoa1908892

4. US Food and Drug Administration accepts for priority review supplemental biologics license application for Reblozyl (luspatercept-aamt) in adults with non-transfusion dependent (NTD) beta thalassemia. News release. Bristol Myers Squibb; December 3, 2021. Accessed December 12, 2021. 

In the MEDALIST analysis that was presented at the 2021 ASH Annual Meeting, investigators sought to further characterize the effects of luspatercept in patients with low-risk myelodysplastic syndrome.

Luspatercept Induces High Response With Tolerable Safety in Low-Risk MDS

Ciltacabtagene autoleucel (cilta-cel) induced objective response in 97.9% of patients with relapsed/refractory multiple myeloma and led to a stringent complete response (sCR) rate of 82.5%, according to updated findings from the phase 1b/2 CARTITUDE-1 trial (NCT03548207) that were presented during the 2021 ASH Annual Meeting.

Additionally, the 2-year progression-free and overall survival (OS) rates were 60.5% and 74.0% in all patients, respectively, and minimal residual disease (MRD) negativity (10-5) was achieved in 92% of evaluable patients for MRD (n = 61). The 2-year progression-free survival (PFS) rates were improved in those who had MRD negativity sustained for at least 6 and 12 months, at 91% and 100%, respectively, as well as the 2-year OS rates at 100% and 100%, respectively.

“These data are encouraging, and they suggest that cilta-cel will be an important treatment option for patients with multiple myeloma,” lead study author Thomas Martin, MD, clinical professor of medicine in the Adult Leukemia and Bone Marrow Transplantation Program, and associate director of the Myeloma Program, of theUniversity of California, San Francisco, said in a presentation on the data.

Cilta-cel is a BCMA-directed CAR T-cell therapy with 2 BCMA-targeting single-domain antibodies that are designed to confer avidity. A biologics license application seeking the approval of the agent is currently under priority review status with the FDA for use in adult patients with relapsed and/or refractory multiple myeloma.

In November 2021, the FDA extended the Prescription Drug User Fee Act target date for the application to review recently submitted data linked with an updated analytical method following an information request that was issued by the agency.

 The new action date is February 28, 2022.

At the prior readout of CARTITUDE-1 data, which had a median follow-up of 12.4 months, the objective response rate with the CAR T-cell therapy was also 98% and the sCR rate was 67%.3 The 1-year PFS and OS rates were 77% and 89%, respectively. Additionally, neither the median PFS (95% CI, 16.8–not estimable [NE]) nor the duration of response (95% CI, 15.9–NE) had been reached.

In the open-label, multicenter, phase 1b/2 CARTITUDE-1 trial, investigators enrolled patients with progressive multiple myeloma as per International Myeloma Working Group criteria, an ECOG performance status of less than 1, who had measurable disease, had received at least 3 prior therapies or were double refractory, and prior exposure to a proteasome inhibitor, immunomodulatory drug (IMiD), and an anti-CD38 antibody.

Following screening and apheresis, patients underwent bridging therapy, if needed, before they received lymphodepletion with cyclophosphamide at 300 mg/m2 and fludarabine at 30 mg/m

, both administered daily for 3 days. Five to 7 days following lymphodepletion, patients were administered a single infusion of the CAR T-cell therapy at a targeted dose of 0.75 x 10

 CAR-positive viable T cells/kg (range, 0.5 x 10

Following the infusion, patients were evaluated for efficacy and safety.

The primary end point in the phase 1b portion of the trial was to characterize the safety of cilta-cel and confirm the recommended phase 2 dose; in the phase 2 portion, the primary end point was to evaluate the efficacy of cilta-cel.

Regarding baseline characteristics for the 97 patients, the median age was 61.0 years (range, 43-78), 58.8% of patients were male, and 17.5% of patients were Black/African American. Moreover, 19.6% of patients had plasmacytomas that were either extramedullary (13.4%) or bone based (6.2%). High-risk cytogenetic profiles were reported in 23.7% of patients, which included del(17p) in 19.6%, t(14;16) in 2.1%, and t(4;14) in 3.1% of patients. Most patients (91.9%) had tumor BCMA expression on at least 50% of cells.

The median number of prior lines of therapy was 6.0 (range, 3-18) and most patients received at least 5 prior therapies (66.0%). Additionally,87.6% of patients were triple-class refractory and 42.3% were penta-drug refractory. Patients were refractory to carfilzomib (Kyprolis; 64.9%), pomalidomide (Pomalyst; 83.5%), and/or an anti-CD38 antibody (99.0%). Nearly all patients (99.0%) were refractory to their last line of therapy, and the median years since diagnosis was 5.9 years (range, 1.6-18.2).

The median administered dose of cilta-cel was 0.71 x 10

CAR + viable T cells/kg (range, 0.51-0.95 x 10

In the longer follow-up that included the 97.9% ORR (n = 95/97), the very good partial response rate or better was 94.9% and the partial response rate was 12.4%. Of the 2 nonresponders, 1 did not have measurable disease at baseline and consequently could not be evaluated for response but is currently in remission; the second patient had evidence of increased lytic disease and did not experience an objective response before that time.

The median time to first response was 1.0 month (range, 0.9-10.7), the median time to best response was 2.6 months (range, 0.9-17.8), and the median time to complete response or better was 2.9 months (range, 0.9-17.8). The median duration of response was still not estimable (21.8 months–NE).

The median PFS was not reached in both all patients (95% CI, 64.3-79.4%) and in those who achieved a sCR (95% CI, 25.2-NE). In patients who achieved a sCR, the 2-year PFS rate was 71.0%. The median OS has also not been reached.

Cilta-cel was also found to have a manageable safety profile, with no new safety signals, including new events of neurotoxicity and neurocognitive treatment-emergent adverse effects, observed with the longer follow-up.

“After implementation of mitigation strategies throughout the CARTITUDE program with more than 200 patients treated, the incidence of movement in neurocognitive AEs has decreased to 0.5%,” Martin, who is also co-leader of the Cancer Immunology & Immunotherapy Program at the UCSF Helen Diller Family Comprehensive Cancer Center, said. “There were no additional treatment-related deaths at 2 years of follow-up.”

Fifteen secondary primary malignancies were previously reported in 11 patients overall, all of which were found to be unrelated to cilta-cel via investigator assessment; 6 of these new secondary primary malignancies (acute myeloid leukemia, myelodysplastic syndrome, and 4 cutaneous) were reported since the median estimated 1 year of follow-up.

“I’ll remind everyone that this was a heavily pretreated population, with all patients having previously being exposed to IMiDs and alkylators, and the majority of patients receiving stem cell transplantation,” Martin added. “These patients are also experiencing unprecedented survival, and thus, I think these rates of secondary malignancy appear consistent with the population that was involved in this study.

Cilta-cel is currently being tested in earlier-line settings for patients with multiple myeloma, as seen in the CARTITUDE-2 (NCT04133636), CARTITUDE-4 (NCT04181827), and CARTITUDE-5 (NCT04923893) studies.

“Outpatient administration of cilta-cel is also being explored in these studies,” Martin concluded.

1. Martin T, Usmani SZ, Berdeja JG, et al. Updated results from CARTITUDE-1: phase 1b/2Study of ciltacabtagene autoleucel, a B-cell maturation antigen–directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma. Presented at: 2021 ASH Annual Meeting; December 11-14, 2021; Atlanta, GA. Abstract 549.

2. US Food and Drug Administration grants BCMA CAR-T cilta-cel priority review for the treatment for relapsed/refractory multiple myeloma. News release. Legend Biotech Corporation; May 26, 2021. Accessed December 13, 2021. 

3. Legend Biotech announces extension of PDUFA date for cilta-cel. News release. Legend Biotech Corporation; November 1, 2021. Accessed December 13, 2021. 

4. Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. 

. 2021;398(10297):314-324. doi:10.1016/S0140-6736(21)00933-8

Updated results from CARTITUDE-1 reveal deep and durable response to ciltacabtagene autoleucel treatment in patients with multiple myeloma. 

Cilta-Cel Shows Further Promises in R/R Multiple Myeloma

Patients with relapsed/refractory large B-cell lymphoma (LBCL) in the phase 3 ZUMA-7 study (NCT03391466) had a 60% improvement in event-free survival (EFS) with axicabtagene ciloleucel (axi-cel; Yescarta)compared with standard-of-care (SOC) chemotherapy in the second-line setting, according to a presentation during the ASH Annual Meeting 2021.

At a median follow-up of 24.9 months, findings showed that the median EFS was 8.3 months (95% CI, 4.5-15.8) for patients on axi-cel compared with 2.0 months (95% CI, 1.6-2.8) for those on SOC chemotherapy (HR, 0.398; 95% CI, 0.308-0.514; 

 < .0001). The 2-year EFS rates in the investigative and control arms were 40.5% (95% CI, 33.2%-47.7%) and 16.3% (95% CI, 11.1%-22.2%), respectively.

EFS was superior with axi-cel over SOC across key patient subgroups, including age (<65 years; HR, 0.490 vs ≥65 years; HR, 0.276), response to first-line therapy at randomization (primary refractory; HR, 0.426 vs relapsed within 1 year of frontline therapy; HR, 0.342), Second-Line Age-Adjusted International Prognostic Index (sAAIPI) stage (0-1; HR, 0.407 vs 2-3; HR, 0.388), and prognostic marker per central laboratory (high-grade B-cell lymphoma [HGBL]-double/triple-hit; HR, 0.285 vs double-expressor lymphoma; HR, 0.424).

“ZUMA-7 met its primary EFS end point, demonstrating statistically significant and clinically meaningful improvement in efficacy with axi-cel vs second-line SOC in relapsed/refractory large B-cell lymphoma,” lead study author Frederick Locke, MD, said in a presentation on the data during the meeting.

“Axi-cel showed superiority over standard of care with over 4-fold greater median EFS, 2.5-fold greater 2-year EFS, a 33% higher objective response rate, double the complete response rate, and EFS improvements across key subgroups,” Locke, who is vice chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center, added. “Results from the ZUMA-7 trial herald a paradigm shift: axi-cel should be a new standard for patients with second-line relapsed/refractory large B-cell lymphoma.”

Currently, standard second-line treatment in the curative setting, is salvage chemotherapy followed by consolidation high-dose therapy (HDT)–autologous stem cell transplant (ASCT). However, most patients are unable to receive HDT-ASCT, and these patients have a poor prognosis.

Axi-cel is an autologous CD19-directed CAR T-cell therapy that is currently FDA approved for the treatment of adult patients with relapsed/refractory LBCL after at least 2 lines of systemic therapy.

ZUMA-7 is the first randomized, international, multicenter, phase 3 trial of axi-cel compared with SOC as a second-line treatment for patients with relapsed/refractory LBCL. A total of 359 patients with relapsed/refractory LBCL across 77 sites were randomized 1:1 to receive axi-cel plus conditioning chemotherapy (n = 180) or SOC with investigator-selected platinum-based chemoimmunotherapy (n = 179). An initial disease assessment was done at day 50; those on axi-cel continued to day 100, day 150, and long-term follow-up. Responders to SOC, either with a complete or partial response, proceeded to HDT-ASCT; nonresponders received additional treatment off of protocol.

To be eligible for enrollment, patients had to be aged at least 18 years of age, have LBCL that was relapsed/refractory within 12 months of frontline therapy, and had intentions to proceed to HDT-ASCT. Stratification factors included response to frontline therapy and sAAIPI.

Steroid-only bridging therapy, without chemotherapy, was optional.

The primary end point of the trial was EFS by blinded central review; key secondary end points are progression-free survival, safety, and patient-reported outcomes. There was no protocol-specified crossover.

Patients were enrolled between January 25, 2018 and October 4, 2019. For the EFS primary analysis, the data cutoff date was March 18, 2021, at which point, 250 events had occurred.

Of the 180 patients randomized to axi-cel, 94% received treatment with the CAR T-cell therapy.

Of those enrolled to the SOC arm (n = 179), 36% of patients received HDT-ASCT.

Baseline characteristics were generally balanced between the 2 arms. Overall, the median age was 59 years (range, 21-81), and 30% of patients were 65 years and older. Most patients (79%) had stage III/IV disease, and 45% of patients had a sAAIPI of 2 to 3. Most patients (74%) were primary refractory to their frontline therapy vs 26% who relapsed within 1 year of their prior treatment. Sixteen percent of patients had high-grade BL (double-/triple-hit) vs 33% who had double-expressor lymphoma and 6% who had 

 rearrangement. Fifty-four percent of patients had elevated lactate dehydrogenase levels.

Additional findings showed that the objective response rate was 83% with axi-cel vs 50% with SOC (odds ratio, 5.31; 95% CI, 3.1-8.9; 

 < .0001). In the axi-cel arm, the ORR consisted of a 65% complete response rate and a 18% partial response rate; these rates were 32% and 18%, respectively, in the SOC arm.

At the time of the interim analysis, the median overall survival (OS) was not reached (95% CI, 28.3–not evaluable [NE]) with axi-cel compared with 35.1 months (95% CI, 18.5–NE) with SOC (HR, 0.730; 95% CI, 0.530-1.007; 

Further data showed that 56% of patients on the SOC arm received subsequent cellular immunotherapy off protocol, and Locke said that a preplanned sensitivity analysis suggests an OS benefit with axi-cel that is likely confounded by SOC treatment switching.

“The primary OS analysis will occur in the future,” Locke noted.

Regarding safety, grade 3 or higher adverse effects (AEs) occurred in 91% of patients on axi-cel compared with 83% of those on SOC, the most common of which included neutropenia (69% vs 41%, respectively), anemia (30% vs 39%), and leukopenia (29% vs 22%). Grade 3 or higher serious AEs occurred in 42% and 40% of patients on axi-cel and SOC, respectively.

Fifty-five deaths occurred on the axi-cel arm, reasons for which included progressive disease (n = 47), grade 5 AE during protocol-specified reporting period (n = 7), and definitive therapy-related mortality (n = 1). This was in comparison to 68 deaths on the SOC arm, with the same reasons occurring in 64, 2, and 2 patients, respectively.

Grade 3 or higher cytokine release syndrome occurred in 6% of patients on axi-cel; the most common any-grade symptoms were pyrexia (99%), hypotension (43%), and sinus tachycardia (31%). CRS was managed by tocilizumab (Actemra; 65%), corticosteroids (24%), and vasopressors (6%). The median time to onset was 3 days and the median duration of events was 7 days.

Grade 3 or higher neurologic events occurred in 21% of axi-cel–treated patients and 1% of SOC-treated patients; the most common symptoms included tremor (26% with axi-cel vs 1% with SOC), confusional state (24% vs 2%, respectively), and aphasia (21% vs 0%). These were all managed by corticosteroids. The median time to onset was 7 days with axi-cel and 23 days with SOC; the median duration of events was 9 days and 23 days, respectively.

Locke also noted that CAR T-cell levels were associated with objective response, and tumor burden impacted complete response rate in the SOC arm.

“Higher tumor burden was associated with decrease likelihood of complete response in the standard-of-care arm,” said Locke. “In contrast, higher tumor burden did not predict for a lower likelihood for complete response in the axi-cel arm.”

Locke F, Miklos DB, Jacobson CA, et al. Primary analysis of ZUMA‑7: a phase 3 randomized trial of axicabtagene ciloleucel (axi-cel) versus standard‑of‑care therapy in patients with relapsed/refractory large B-cell lymphoma. Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 2.

Phase 3 ZUMA-7 study results indicate that axicabtagene ciloleucel may achieve longer event-free survival compared with standard chemotherapy.

Axi-Cel Prolongs Event-Free Survival in Second-Line Relapsed/Refractory LBCL

Patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS) had higher mortality rates after being diagnosed with COVID-19 than those with COVID-19 who did not have cancer, according to data from the American Society of Hematology Research Collaborative (ASH RC) Data Hub for Hematology.

The overall mortality rate from COVID-19 in the cohort of 257 patients with AML/ALL/MDS was 21%. Sixty percent of patients overall were hospitalized for COVID-19 infection; 1% of patients who died did not require hospitalization for COVID-19 compared with 34% who did. In patients who went to the intensive care unit (ICU), the mortality rate was 68%.

Additionally, the findings, which were presented during the 2021 ASH Annual Meeting, indicated that patients with both active disease and neutropenia at diagnosis were more likely to experience severe COVID-19 infection. However, those with active disease were not found to have increased mortality from the virus.

“The 2 factors that did impact COVID-19 mortality was having a primary disease prognosis of less than 6 months and deferral of ICU,” lead study author Pinkal Desai, MD, an assistant professor of medicine at Weill Cornell Medical College and assistant attending physician at NewYork-Presbyterian Hospital, said in a press briefing during the meeting. “Among hospitalized patients only, those with a pre–COVID-19 prognosis of less than 6 months and ICU deferral had higher COVID-19 mortality.”

Data are currently lacking on predictors of severe infection and outcomes with COVID-19 in patients with AML, ALL, and MDS. However, it is believed that those with active disease may experience poorer outcomes because of cytopenias and their overall prognosis. Additionally, Pinkal noted that single-center studies have demonstrated higher rates of COVID-19 infection severityand mortalityin patients with acute leukemia.

With the ASH RC Data Hub for Hematology, investigators sought to identify risk factors for severe COVID-19 infection and mortality in patients with AML, ALL, and MDS by utilizing the ASH RC COVID-19 Registry for Hematology.

The registry comprises the features and outcomes of confirmed or presumptive COVID-19 diagnoses in adult patients with ongoing or a history of hematologic disorders. Data collection was opened internationally on April 1, 2020, through a platform hosted by Prometheus Research, with data regularly updated on the ASH website.

Investigators analyzed patient characteristics, outcomes, and predictors, and stratification factors included disease status (active initial diagnosis vs relapsed/refractory vs remission) and type of hematologic cancer; variables were age, comorbidities, type of hematologic cancer (AML, ALL, or MDS), neutrophil and lymphocyte count, and active treatment at time of COVID-19 diagnosis. COVID-19 severity was considered mild (no hospitalization), moderate (hospitalization), or severe (ICU admission).

The primary end point of the research was mortality from COVID-19; COVID-19 severity served as a secondary end point.

Data comprised 257 patients overall with AML (n = 135; 53%), ALL (n = 82; 32%), and MDS (n = 40; 16%); 46% of patients were in remission and 44% had active disease; 10% of patients had unknown status. Nearly half (49%) of patients were younger than 60 years, 55% were male, and most patients (74%) had a major comorbidity. Seventy-five percent of patients had received systemic therapy in the previous year, and 72% had an estimated prognosis of more than 6 months. Also, most patients (78%) did not have deferred ICU.

Patients with acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome had higher mortality rates after being diagnosed with COVID-19 than those with COVID-19 who did not have cancer.