Ryan McDonald

In patients with previously untreated, locally advanced stage III non–small cell lung cancer (NSCLC) treated with pembrolizumab (Keytruda) plus concurrent chemoradiation followed by pembrolizumab monotherapy, therapy continued to be efficacious after longer follow-up, according to updated findings from the KEYNOTE-799 trial (NCT03631784).

Findings also demonstrated that treatment with the study regimen led to 2-year progression-free survival (PFS) rates of 55.3% in patients with squamous and nonsquamous histology (cohort A) and 60.6% in patients with nonsquamous histology only (cohort B).

Moreover, the overall survival rate at 2 years was 64.3% in cohort A and 71.2% in cohort B.

The typical standard of care for patients with unresectable, stage 3 NSCLC consists of concurrent chemoradiation followed by consolidation therapy with durvalumab (Imfinzi), according to the study authors.

Here, the investigators presented additional findings from the KEYNOTE-799 trial. Previous results from a primary analysis of the data with a cutoff date of Oct. 28, 2020, showed that cohort A (n = 112) had an overall response rate (ORR) of 70.5% and cohort B achieved an ORR of 70.6%. At the time of the primary analysis, a small proportion of cohort A (8.0%) and cohort B (6.9%) experienced grade 3 or worse pneumonitis.

The updated findings include an additional 1-year of follow-up for all enrolled patients.

To be enrolled onto KEYNOTE-799, patients had to be aged 18 years or older, have stage 3A-C, unresectable, locally advanced, pathologically confirmed, previously untreated NSCLC. Patients were not permitted to have received prior systemic immunosuppressive therapy within 7 days of enrollment. In total, 216 patients enrolled onto the trial, however only 214 received treatment.

Patients in cohort A (n = 112; median age, 66 years) received 200 mg of pembrolizumab every 3 weeks (Q3W) plus 200 mg/m2 of paclitaxel Q3W and carboplatin AUC6 Q3W during the first cycle. From treatment cycles 2-3, the cohort received the same dosage of pembrolizumab as well as 45 mg/m2 of paclitaxel once weekly (QW) plus carboplatin AUC2 QW and thoracic radiotherapy (60 Gy in 30-daily, 2-Gy fractions 5 days a week). This was then followed by 200 mg of pembrolizumab Q3W until cycle 17 was completed or disease progression, unacceptable adverse events (AEs), illness that prevented further treatment or study withdrawal.

Cohort B (n = 102; median age, 64 years) received a slightly different regimen. Patients in this cohort received pembrolizumab 200 mg Q3W plus pemetrexed 500 mg/m2 Q3W and 75 mg/m2 of cisplatin Q3W during cycle 1. Cycles 2-3 consisted of the same treatments and doses with thoracic radiotherapy added to the regimen. And then for cycles 4-17, patients received 200 mg of pembrolizumab Q3W until the last cycle was completed or any occurrence that would result in treatment withdrawal.

With an added year of follow-up, the ORR in both overall patient populations increased slightly — 71.4% (95% CI, 62.1-79.6) in cohort A and 75.5% (95% CI, 66.0-83.5) in cohort B. In terms of ORR by cancer stage, patients with stage 3A derived the most benefit — 73.2% (95% CI, 57.1-85.8) in cohort A and 76.9% (95% CI, 60.7-88.9) in cohort B.

Patients with an ongoing response to treatment dropped from 78.8% at 12 months to 64% at 24 months in cohort A. There was also a decrease in cohort B, but not as significant (74.8% vs 68.7%, respectively).

In terms of treatment-related AEs, 93.8% of cohort A and 97.1% of cohort B experienced an event at any grade.

“Pembrolizumab plus [concurrent chemoradiation therapy] followed by pembrolizumab represents a promising therapy for patients with previously untreated, locally advanced, stage 3 NSCLC,” the study authors concluded.

Reck M, Lee KH, Frost N, et al. Two-year update from KEYNOTE-799: Pembrolizumab plus concurrent chemoradiation therapy (cCRT) for unresectable, locally advanced, stage III NSCLC. 

. 2022;40(suppl 16):8508. doi:10.1200/JCO.2022.40.16_suppl.8508

Articles

In patients with previously untreated, locally advanced stage III non–small cell lung cancer, continued benefit from pembrolizumab with concurrent chemoradiation followed by additional pembrolizumab was observed after more than 2 years of follow-up.

KEYNOTE-799 Results Reveal Durable Responses in Previously Untreated Stage III NSCLC

Results of the phase 1/2 LUPER study (NCT04358237) showed the combination of lurbinectedin (Zepzelca) and pembrolizumab (Keytruda) in the second-line to be associated with a manageable safety profile and early efficacy in a small population of patients with relapsed small-cell lung cancer (SCLC), according to findings presented at the 2022 American Society of Clinical Oncology.

Treatment with lurbinectedin plus pembrolizumab resulted in an overall response rate (ORR) of 30.8% among the 13 patients [median age, 66 years (range, 43-78); 54% male] enrolled onto the trial across 3 hospitals in Spain.

As of March 10, 2022, 4 patients remained on treatment. The preliminary findings showed that the median duration of treatment was 3.1 [range, 0-14.6] months. Moreover, a median duration of response (DOR) has not yet been reached. Seventy-five percent of patients were shown to derive a response to treatment at 9 months [95% CI; 42.6%-100%).

Previously, the Food and Drug Administration (FDA) 

 for the treatment of adults with metastatic SCLC with disease progression on or following platinum-based chemotherapy.

Those findings demonstrated that lurbinectedin monotherapy demonstrated an ORR of 35% and a median DOR of 5.3 months per investigator assessment.

Here, the study authors presented preliminary data from the early-phase trial that, according to the investigators, is assessing the safety, tolerability and efficacy of lurbinectedin plus pembrolizumab in this patient population for the first time.

Enrolled patients have to be aged 18 years or older, have an ECOG Performance Status of 0-1 and have measurable disease per RECIST v.1.1. Additionally, patients must have had progression to a chemotherapy-containing regimen at least 4 weeks prior to enrolling into the study.

Patients were excluded from enrollment if they had received prior treatment with an immunotherapy. However, patients with stable, asymptomatic and treated brain metastases are allowed onto the trial.

The aim of the phase 1 portion of the trial was to identify a maximum tolerated dose as well as the recommended phase 2 dose of the combination treatment. As for the phase 2 portion of the trial, the goal is to analyze efficacy of the study treatment per ORR. Additional endpoints include safety, preliminary efficacy and the pharmacokinetics of the combination.

Patients enrolled into the phase 1 trial were administered 200 mg of pembrolizumab every 3 weeks (Q3W) plus a starting dose of 2.4 mg/m2 of lurbinectedin Q3W. A grade 3 fatigue occurred in the phase 1 portion of the trial. That adverse event (AE) caused the patient to have a dose reduction.

After further evaluation, the investigators identified the recommended phase 2 dose as 3.2 mg/m2 of lurbinectedin and 200 mg of pembrolizumab administered Q3W.

Early results showed that 84.6% of the population reported experiencing an any-grade treatment-emergent AE. The most common TEAE that was hematologic was neutropenia (53.9% any grade). Fatigue of any-grade severity (76.9%) was the most common non-hematologic TEAE. Of note, there was one patient death, however it was attributed to COVID-19.

“This combination warrants further confirmation in the ongoing expansion phase 2 [trial] with additional biomarker analysis of efficacy,” the study authors concluded in a poster detailing the findings.

1. Calles A, Navarro A, Doger B, et al. A phase 1/2 trial of lurbinectedin (L) in combination with pembrolizumab (P) in relapsed small cell lung cancer (SCLC): The LUPER study. 

. 2022; 40 (suppl 16):8581. doi: doi.10.1200/JCO.2022.40.16_suppl.8581

2. Jazz Pharmaceuticals announces U.S. FDA accelerated approval of Zepzelca™ (lurbinectedin) for the treatment of metastatic small cell lung cancer. News Release. AstraZeneca. June 15, 2020. https://yhoo.it/3NXrJ0y

Lurbinectedin in combination with pembrolizumab in the second-line shows promising safety and efficacy in relapsed small cell lung cancer

Second-line Lurbinectedin Plus Pembrolizumab is Safe and Effective in Relapsed SCLC

In the phase 3 ELEVATE-TN study (NCT02475681), patients with treatment-naïve chronic lymphocytic leukemia (CLL) who received treatment with acalabrutinib (Calquence) either as a single-agent or in combination with obinutuzumab (Gazyva) continue to achieve better treatment outcomes long-term compared with those who were administered obinutuzumab plus chlorambucil, according to results of presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

Prior results of the ELEVATE-TN study show a median follow-up of 28.3 and 46.9 months of acalabrutinib with or without obinutuzumab induced superior efficacy than the chemoimmunotherapy combination of obinutuzumab and chlorambucil.

Jeff Sharman, MD, director of research, Willamette Valley Cancer Institute, medical director of hematology research, The US Oncology Network, presented the updated findings.

Enrolled patients (n = 535) were aged 65 years and older, or between 18 to 65 years with certain comorbidities.

Patients (median age, 70 years) were randomized to receive either single-agent acalabrutinib (n = 179), acalabrutinib with obinutuzumab (n = 179) or the chemoimmunotherapy combination (n = 177). Patients enrolled into the chemoimmunotherapy arm were permitted to crossover to the acalabrutinib single-agent arm once study authors confirmed disease progression.

Measuring progression-free survival (PFS) was the primary endpoint of ELEVATE-TN. Sharman noted that at the 58.2-month mark (range: 0.0-72.0 months), 59.8% and 64.8% of patients in the acalabrutinib single-agent and acalabrutinib plus obinutuzumab arms remained on treatment, respectively. Moreover, 72 patients who started the trial in the chemoimmunotherapy arm have crossed over to receive single-agent acalabrutinib. Since crossing over, 25% of patients have discontinued single-agent treatment — 10% of discontinuations were due to adverse events (AEs).

As of this reporting, PFS outcomes favor single-agent acalabrutinib (72%) and acalabrutinib plus obinutuzumab (84%) versus the chemoimmunotherapy regimen (21%). Moreover, a median PFS has not yet been reached for either acalabrutinib arm whereas it is 27.8 months in the chemoimmunotherapy arm.

The findings also demonstrated that the PFS benefit translated to patients who had del(17p) and/or mutated 

. In this patient population, both the acalabrutinib only and acalabrutinib plus obinutuzumab arm have a PFS rate of 71%. The PFS rate drops significantly to 18% in the chemoimmunotherapy arm.

Overall response rate (ORR) was also significantly higher in both the acalabrutinib plus obinutuzumab (96.1%; 

= .0499) arms compared with the chemoimmunotherapy combo (83.1%). Complete responses also occurred more frequently in the acalabrutinib-containing arms — 32.4% and 14.5% in the acalabrutinib combination and single-agent arm, respectively. Whereas 13.6% of patients in the chemoimmunotherapy arm achieved a complete response.

“The proportion of patients who achieved a complete response, including those with incomplete blood count recovery, were higher in the acalabrutinib-containing arms,” Sharman said during a pre-recorded presentation of the data. “Minimal residual disease was completed only for those patients who achieved complete response.”

Forty-two percent of the patients who achieved a complete response with acalabrutinib plus obinutuzumab had undetectable minimal residual disease (MRD), versus 9% of patients in the chemoimmunotherapy arm.

A median overall survival has not yet been reached in any of the treatment arms, according to Sharman. However, he said, the authors have observed longer overall survival in the acalabrutinib plus obinutuzumab arm versus the chemoimmunotherapy arm.

In terms of adverse events, Sharman said they remained similar to past analyses of the findings. Cardiac events, bleeding and infections were significantly more likely to occur in both acalabrutinib treatment arms versus the chemoimmunotherapy arm. However, Sharman noted these were also consistent with what has been previously shown.

“We conclude that acalabrutinib demonstrates durability, tolerability, and flexibility to tailor treatment as monotherapy or in combination with obinutuzumab in patients with treatment-naive chronic lymphocytic leukemia,” he said of the findings.

Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: Five-year follow-up of ELEVATE-TN. J

. 2022;40(suppl 16):7539. doi: 10.1200/JCO.2022.40.16_suppl.7539

With roughly 5 years of follow-up, outcomes were more favorable with acalabrutinib with or without obinutuzumab vs obinutuzumab and chlorambucil in patients with treatment-naïve chronic lymphocytic leukemia.

Acalabrutinib-Based Regimens Continue to Top Obinutuzumab Plus Chemotherapy in Treatment-Naïve CLL

Not all patients with cancer have derived benefit from the ease of access of telemedicine, eventhough the use of telemedicine for cancer care grew significantly during COVID-19, as compared with its usage before the start of the global pandemic.

Newly released study findings — which were presented during a press briefing ahead of the 2022 ASCO Annual Meeting — demonstrated that despite the increased use in telemedicine among patients across more than 20 cancer types, inequities in its usage remain.

“The COVID-19 pandemic was associated with disruptions in healthcare delivery, including substantial declines in personal clinical visits,” lead study author Jenny S. Guadamuz, PhD, a postdoctoral research fellow, USC Program on Medicines and Public Health, USC School of Pharmacy, said during a presentation of the data. “And as a result, many clinicians shifted to telemedicine services, and this was facilitated by federal and state regulations enacted early in the pandemic that expanded coverage and reimbursement for these services. And while there's some evidence suggesting that telemedicine uptake varied by social demographic factors such as age and region, there has been limited evaluation of inequities.”

To investigate the inequities associated with telemedicine use by race, ethnicity and social determinants of health, the study authors analyzed electronic health records from a Flatiron Health database.

They reviewed the records of 26,788 people aged 18 years and older who started their first-line of cancer treatment between March 2020 and November 2021. The patients included in the analysis had to have had received follow-up care within 90 days and been treated at a community-based oncology practice.

The findings were adjusted using patient clinical characteristics including age, sex, performance status and the stage of their disease.

Of the patients included in the analysis, 16.0% used telemedicine services.

The investigators identified that telemedicine use was notably lower in Black patients when compared with their White counterparts (13.2% versus 15.6%, respectively). Additionally, patients without documented insurance were less likely than patients who had private insurance or were insured through Medicare to use telemedicine services during the same time period (11.8% versus 16.4%).

The largest disparity in telemedicine use was in people based on socioeconomic status —10.6% of patients living in the lowest socioeconomic status areas partook in telemedicine care compared with 23.6% of patients in areas with the highest socioeconomic status.

Guadamuz stressed that the inequities remained after the investigators adjusted for clinical characteristics.

“We found that black patients had lower odds of telemedicine of using telemedicine services in both unadjusted and adjusted models,” she said. “In other words, clinical characteristics do not account for these differences.”

And although their findings demonstrated that telemedicine use waned as the pandemic progressed (25% from March to May 2020 versus 12% from Sept. to Nov. 2021), the inequities persisted.

“These findings are critically important considering recent efforts to make coverage for telemedicine services permanent instead of being tied to the HHS public health emergency declaration,” she said. “There (are) also efforts to increase reimbursement rates for telemedicine services by Medicare, several Medicaid programs and private insurers.”

The most important conclusion from these findings, according to Guadamuz, is that this disparity access and use to telemedicine services may further widen the inequity gap in cancer care.

For instance, she explained, it should not be assumed that every patient has equitable access to the necessary infrastructure — such as high-speed internet — to utilize telemedicine services.

Guadamuz noted that there are several things to keep in mind for future research. One thing she said was to see if there’s any differences in the timely receipt of necessary treatment between patients who received telemedicine care and those who received in-person care. Moreover, it is important to learn from the centers that have successfully utilized telehealth services.

“It'll be important to determine what types of practices are providing telemedicine more equitably to their patients, because we can learn from these clinics and bring it back to the rest of the of our network of clinics, therefore supporting more affordable care at community-based oncology clinics,” Guadamuz concluded.

Use of Telemedicine for Cancer Care Increased, but Varied by Race, Socioeconomic Status, and Other Factors During the COVID-19 Pandemic. News Release. ASCO. May 26, 2022. Accessed May 26, 2022. https://bit.ly/3wPFVD9

Disparities Persist With Telemedicine Use in Cancer Care 

Lenvatinib (Lenvima) in combination with pembrolizumab (Keytruda) demonstrated clinical benefit in patients with advanced renal cell carcinoma (aRCC) regardless of their biomarker status, according to data from an exploratory analysis of the KEYNOTE-146/study 111 trial presented at the 2022 ASCO Genitourinary Cancers Symposium.

Although the study results were “disappointing from a biomarker development standpoint,” according to lead study author Chung-Han Lee, MD, PhD, assistant attending physician, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, the results confirm the effectiveness of the regimen across various lines of treatment.

“We know that even without biomarker stratification, this regimen already has high response rates and a fairly long progression-free survival,” Lee said in an interview with 

. “[Providers] don't necessarily need to do extra steps in order to make a decision about whether or not they would offer this type of treatment to their patients.”

The primary objective of the analysis was to identify if there was an association between patient outcomes and gene expression signatures generated via RNA sequencing and DNA variants for individual genes of interest via whole exome sequencing. As of now, Lee explained, the field is in its infancy stages in learning if there are good predictive biomarkers to stratify patients to different treatment modalities.

“What we’ve done already is we’ve looked at various genomic and gene expression biomarkers in various settings. A lot of this comes from analysis of both phase 2 and phase 3 studies. Perhaps the most informative (data) recently has been looking within the first-line space,” he said. “And what they've demonstrated is there are specific gene expression patterns that have correlated with superior outcomes. However, where we really are lacking is the ability to translate this into clinical practice and having this type of information guide some of the clinical choices that we're making.”

In the past, providers have been able to analyze the genomics of patients who were naive to immunotherapy and identify those high levels of HLA diversity were linked to an increased odds of response to lenvatinib plus pembrolizumab.

In this exploratory analysis, Lee said, the study authors were interested in seeing if this could be translated in patients who have been pretreated with immunotherapy.

“We're trying to understand whether or not treatment-naive tissue, can be predictive of outcomes for people who've already had multiple lines of systemic therapy,” he explained. “So, we're trying to answer…whether or not there were good predictive biomarkers in the space and whether or not we could use older tissue? Or do the treatments that people have, potentially have an impact on whether or not some of the things that have worked can still continue to work?”

The phase 1b/2 KEYNOTE-146/study 111 trial comprised 147 patients (median age, 60 years; 78.2% male; 86.5% White), of which 80 (median age, 62 years; 75% male; 92.5% White) had available RNA sequencing and 60 had available whole exome sequencing (median age, 63.5 years; 78.3% male; 90% White).

A significant proportion of patients (71.4%) in the overall population had received prior anti–PD-1/PD-L1 therapy, as did patients in the RNA-sequencing population (87.5%) and whole exome sequencing population (88.3%). Few patients in the overall population, RNA-sequencing and whole exome sequencing population were treatment naïve (15.6%; 12.5%; 11.7%, respectively).

The findings showed that the objective response rate was similar among the 3 patient subgroups — 63.9% in the overall population, 66.2% in those with evaluable RNA sequencing and 68.3% in those with evaluable whole exome sequencing.

Moreover, the median PFS was also similar across the 3 groups. The median PFS in the overall population was 14.1 months (95% CI, 11.7-18.6), and 17.7 months in both the RNA-sequencing evaluable group (95% CI, 11.1-19.8) and the whole exome sequencing-evaluable group (95% CI, 11.7-22.1). The data also showed similar objective response rates across selected DNA variants including 

As for next steps, Lee noted that more analyses are warranted.

“It really is going to be looking to see whether or not we can get tissue that is closer to the time of systemic therapy and doing an analysis to see whether or not that is going to end up being predictive,” he concluded. “We certainly also want to see our ability to understand what are the changes that happened to the tumor as [a patient] gets treatment, because that may be very informative in terms of what the subsequent therapies you should think about.

1. Lee CH, Rasco DW, Rao A, et al. Association between biomarkers and clinical outcomes of lenvatinib + pembrolizumab in advanced renal cell carcinoma (RCC): Results from Study 111/KEYNOTE-146. J Clin Oncol. 2022;40(suppl 6):375. doi: 10.1200/JCO.2022.40.6_suppl.375.

Lenvatinib in combination with pembrolizumab demonstrated clinical benefit in patients with advanced renal cell carcinoma regardless of their biomarker status.

Lenvatinib Plus Pembrolizumab Showed Benefit in aRCC With or Without Biomarkers

In patients with t(11;14) relapsed/refractory multiple myeloma (RRMM), venetoclax (Venclexta) at either 400 mg or 800 mg plus daratumumab (Darzalex) and dexamethasone elicited deep durable responses and showed a tolerable safety profile, according to preliminary results of an expansion cohort from a phase 1/2 study (NCT03314181).

“Venetoclax, daratumumab and dexamethasone, as we previously published, continues to demonstrate safety consistent with a known safety profile with no treatment-emergent deaths,” lead study author Jonathan L. Kaufman, MD, medical director, and section chief of Winship Cancer Institute Ambulatory Infusion Centers, said during a presentation of the data at ASH Annual Meeting 2021. “Venetoclax, daratumumab, and dexamethasone leads to deep responses, including a greater number of patients achieving a (very good partial response) and MRD negativity at least 10 to the minus 5, and to date, the preliminary efficacy continues to be consistent.”

These data that were from part 3 of the phase 1/2 study, while earlier results from part 1 of the study demonstrated that treatment with venetoclax, daratumumab, and dexamethasone (VenDd) was associated with a tolerable safety profile and overall response rate (ORR) of 95.8%.2 Moreover, part 2 of the study showed that Venetoclax plus daratumumab, bortezomib (Velcade; V) and dexamethasone induced a similar safety profile and conferred an ORR of 91.7% in patients with RRMM, regardless of t(11;14) status.

In part 3, Kaufman and colleagues wanted to analyze the safety and efficacy of venetoclax at 2 different doses — 400 mg and 800 mg — plus daratumumab and dexamethasone. Part 3 also included a group of patients who received DVd to act as a control to help the researchers properly interpret safety and efficacy.

Patients were randomized in a 4:2:5 fashion.

“The initial studies had more patients at the 800-milligram (dose) and we wanted to learn more about the 400-milligram dose in this study, hence the (randomization) numbers,” Kaufman said.

He noted that venetoclax, regardless of the dosing, was given continuously throughout the study, and daratumumab was administered subcutaneously on its regular schedule. Patients also received 40 mg of dexamethasone on a weekly basis. Patients in the bortezomib-included arm received the triplet therapy in regimens previously noted.

Evaluating the safety and efficacy of VenDd at the 400 and 800 mg dosing levels was the primary endpoint of the study.

Enrolled patients had to be aged 18 years or older, have t(11;14) RRMM, an ECOG performance status 0, 1 or 2, be non-refractory to proteasome inhibitors, non-refractory to anti-CD38 antibodies and received at least 1 prior line of therapy including an IMiD. Moreover, enrolled patients had to have standard adequate hematologic, renal and hepatic function.

Patients, however, were excluded from enrollment if they had prior treatment with venetoclax or any other BCL-2 inhibitors, if they had significant peripheral neuropathy, recent autologous transplant, or any allogeneic transplant, prior anti-CD38 therapy within 6 months prior to the first dose of study drug, and depending on the drug, a washout period of other anti-myeloma treatments 2-6 weeks prior to study enrollment.

Although the study accrual is not yet complete, the results presented at ASH included 15 patients in the Ven400Dd arm, 7 in the Ven800Dd arm and 19 patients in the DVd arm. Patients in both the Ven400Dd arm (range, 1-6) and Ven800Dd arm (range, 1-4) had received a median of 1 prior line of therapy, compared with 2 in the DVd arm (range, 1-4).

Kaufman noted that he anticipates that number will be matched by the time study accrual has been completed.

Moreover, 46.7% of the patient’s in the Ven400Dd arm, 28.6% in the Ven800Dd arm and 42.1% in the DVd arm had received a prior stem cell transplantation. Fourteen patients (93.3%) in the Ven400Dd arm, all patients in the Ven800Dd arm and 17 patients (89.5%) in the DVd arm received a prior proteasome inhibitor. All patients in both the Ven800Dd and DVd arm, as well as 93.3% of patients in the Ven400Dd arm, received a prior IMiD.

There have been no treatment-emergent deaths in this portion of the study, and as of the presentation of the data, 14 of the 15 patients in the Ven400Dd arm and all patients in the Ven800Dd arm remain on the study drug. Seven patients in the DVd arm have discontinued treatment, 6 of which were because of disease progression.

Toxicities were similar between the 3 treatment groups, according to Kaufman. All patients in the DVd arm experienced any grade treatment-emergent adverse event (TEAE) compared with 87% in the Ven400Dd group and 86% in the Ven800Dd arm. Some of the most common AEs that occurred in 20% or more of patients included, but were not limited to, insomnia, fatigue and diarrhea.

Similar differences were also observed regarding infections between the three groups. Grade 3/4 infections occurred more often in the Ven400Dd (13%) and Ven800Dd (14%) group than in the DVd (6%) group.

As far as efficacy, the ORR in the venetoclax groups, as Kaufman expressed, were “very high.” Patients in the Ven400Dd group achieved an ORR of 87% compared with 86% in the Ven800Dd group and 63% in the DVd group. Of note, 72% of the responses in the Ven800Dd group were considered VGPRs.

At the time of presentation of the preliminary results, the median time on treatment in the Ven400Dd group was 6.0 months (range, 0.2-16.5), 8.5 months (range, 1.8-15.9) in the Ven800Dd and 3.9 months (range, 0.5-14.8) in the DVd group.

“We are currently in development of a randomized phase 3 study to confirm these preliminary results,” Kaufman concluded.

1. Kaufman JL, Quach H, Baz R, et al. Safety and Preliminary Efficacy from the Expansion Cohort of a Phase 1/2 Study of Venetoclax Plus Daratumumab and Dexamethasone Vs Daratumumab Plus Bortezomib and Dexamethasone in Patients with t(11;14) Relapsed/Refractory Multiple Myeloma. Presented at 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, Georgia. Abstract 817.

2. Bahlis NJ, Baz R, Harrison SJ, et al. Phase I study of venetoclax plus daratumumab and dexamethasone, with or without bortezomib, in patients with relapsed or refractory multiple myeloma with and without t(11;14). J Clin Oncol. Published online August 13, 2021. doi:10.1200/JCO.21.00443.

Venetoclax dosed at either 400 mg or 800 mg in combination with daratumumab and dexamethasone showed promising preliminary results in a phase 1/2 study.