Hurdles imposed by payers and high drug costs present increasing barriers to technological and precision medicine advancements in cancer programs, according to a recent survey by the Association of Community Cancer Centers (ACCC). Still, telehealth and other new treatment modalities continue to play an increasingly larger role in cancer care in easing administrative burden and broadening access to patient care.

The ACCC&rsquo;s 2018 Trending Now in Cancer Care annual survey included responses from 205 cancer institutions, with hospitals and medical centers collectively representing the majority (89%) of those surveyed. Independent and freestanding cancer centers made up 11% of the total.

&ldquo;The [survey] provides much-needed perspective on strengths and challenges experienced by cancer programs across the country,&rdquo; Thomas A. Gallo, MS, MDA, president of the ACCC, said in a statement. This year marks the release of the ninth annual ACCC survey designed to identify current and emerging trends across cancer programs nationwide.

Telehealth is a widely acknowledged term for the use of digital information and communication technologies intended for remote access to healthcare services. These are thought to save money associated with cancer care while enabling oncologic services to be delivered in communities that lack specialized care. According to the report, telehealth is establishing a strong foothold in oncology care.

&ldquo;Telehealth has tremendous potential for our cancer programs,&rdquo; Mark S. Soberman, MD, MBA, FACS, immediate past president of ACCC, said in an interview with

. &ldquo;It is a way to provide services at a lower cost with less resources...and I do not think there is any disagreement that it is worth pursuing and can create value.&rdquo;

Currently, the most popular services under telehealth include genetic counseling (35%), oral chemotherapy adherence education and support (20%), and symptom management consults (19%). Survey respondents said they plan to provide further services within the next 2 years, primarily in survivorship visits (33%), genetic counseling (29%), oral chemotherapy adherence education and support (48%), and symptom management consults (28%).

Many cancer programs, however, reported challenges in fully implementing telehealth. The majority (70%) of respondents said they struggled with reimbursement issues as well as staff shortages, inadequate technology, and other operational challenges (64%). Less than half (41%) of the cancer programs said they did not have sufficient capital to invest in telehealth technology.

According to Soberman, payers have been slow to align reimbursement policies with the clinical needs of telehealth. &ldquo;It is great that we can provide care in a lower-cost setting without compromising the quality of care, but if we are penalized in terms of reimbursement, it can create problems for sustainability,&rdquo; he said.

Electronic health records (EHRs)designed to broaden access to patient care information&mdash;are another innovative treatment modality that the majority (69%) of cancer centers said &ldquo;significantly improved&rdquo; or &ldquo;somewhat improved&rdquo; their care coordination.

Limitations persist with EHRs, however, and hoped-for efficiency remains unrealized. Nearly 70% of the survey respondents agreed that EHRs have lengthened the workdays of physicians and staff members. This has either &ldquo;significantly worsened&rdquo; or &ldquo;somewhat worsened&rdquo; the well- being of providers, according to 59% of the cancer programs who responded to the survey.

Nearly all respondents (97%) reported interoperability challenges with EHRs, including the limited ability to transmit patient care infor- mation to other systems. Additionally, a lower percentage (41%) of survey respondents said that EHRs have a negative impact on providerpatient interactions during appointments, and a quarter (26%) said that EHRs negatively affect physician and staff retention.

&ldquo;Many of the enterprise EHRs that are used by health systems are not oncology specific or do not have an efficient oncology module,&rdquo; added Soberman. &ldquo;Order entry and clinical data are important in oncology, and they may not be captured by current EHRs.&rdquo; He said the software vendors could be to blame for many of the hurdles of EHRs listed by the cancer programs because they have not fully understood how physicians interact with their products.

Among difficulties cited in growing practices, prior-authorization hurdles established by payers were cited by 48% of the respondents. The cost of drugs and new treatment modalities was also noted as a top inhibitor by 48% of the participants, followed closely by uncertainties in drug pricing reform policies (40%), workforce planning (36%), and marketplace competition (36%).

Barriers to payment and the cost of drugs have hindered nearly three-fourths (72%) of cancer practices from offering immunotherapy treat- ments to their patients, according to the survey. Sixty-three percent of the cancer programs said that payer prior-authorization requirements, including the Center for Medicare & Medicaid Services&rsquo; (CMS) 14-day rule, were one of the largest barriers to biomarker testing for patients. Under the CMS rule, cancer programs cannot bill Medicare for specific molecular testing ordered less than 14 days after a patient who receives outpatient care is discharged from their practice.

&ldquo;While precision medicine is the future of cancer treatment and offers the promise of improved patient outcomes, cancer care providers face numerous challenges delivering this type of care to their patients,&rdquo; the report said. Other barriers to molecular testing included in the survey were concerns about payment (68%) and insufficient protocols for collecting adequate tissue samples (37%).

Seventy-nine percent of cancer programs reported they were either somewhat or very concerned that patients with cancer would refuse treatment because of financial worries. According to the report, almost half (49%) of the survey respondents cited an instance of a patient with cancer who had refused treatment within the previous 12 months.

Another major barrier to precision medicine addressed in the survey was the initiation of clinical trials. The cancer programs reported that among patient-driven challenges, lack of patient understanding of the clinical trial process (66%), lack of patient awareness of clini- cal trial options (56%), and patient concerns about historical stigma related to clinical trials (37%) were 3 major inhibitors.

Practice challenges cited included program infrastructure needs (58%), such as access to technology to identify patients eligible for treatment and tracking outcomes; staff resources and training (55%); and physician engagement and awareness (46%).

Concerns about workflow inefficiencies (75%), heavy workload (67%), and lack of worklife balance (46%) ranked highest among the cancer practice respondents and were the same concerns expressed by their staff members. Also, 38% of those polled said staff turnover was a problem at their cancer program.

Almost half (45%) of the respondents reported turnover of advanced practitioners within the previous 12 months. Advanced practitioners were defined mainly as nurse practitioners (87%), followed by physician assistants (42%) and clinical nurse specialists (15%).

Cancer programs reported that most nurses left for personal reasons (56%); however, additional reasons included compensation (34%), inflexible scheduling (20%), and nurse-to-patient ratios (17%). A high percentage of practices said their daily nurse-to-patient ratio was 1:6 or 1:4 (18% for both), 1:3 (12%), and 1:5 (10%). Eleven percent of the respondents were unsure of the ratio.

According to Soberman, work burden could be alleviated with multidisciplinary teams in cancer practices. &ldquo;We need to organize care in a way that limits the burden on our providers. With multidisciplinary teams, providers can do the things they do best and have others team members do what they do best,&rdquo; he said, adding that EHRs and better ways of documenting care could also minimize activities not related to caregiving.

Advanced practitioners were reported as being heavily engaged in the symptom management of patients (95%) and follow-up patient visits in the outpatient clinic (88%). Additionally, nurse navigators (16%) ranked as the most popular supportive care staff among the cancer programs.

According to the survey, however, most supportive care services are not reimbursed by payers but are instead paid for out of the organiza- tion&rsquo;s operating budget, followed by funds raised by the organizations in the form of grants, corporate gifts, and individual donors.

Symptom management (36%), care coordination (45%), and an increase in the number of subspecialists (44%) were the top 3 invest- ments likely to yield a return. Many cancer program participants (38%) have already put these initiatives into motion in the form of an urgent symptom management clinic, which some said will be added to their practice within the following 2 years.

Association of Community Cancer Centers 2018 survey finds multiple barriers to cancer program growth [news release]. Rockville, MD: Association of Community Cancer Centers; January 17, 2019. prnewswire. com/news-releases/association-of-community-cancer-centers-2018-survey-finds-multiple-barri- ers-to-cancer-program-growth-300780021.html?tc=eml_cleartime. Accessed January 18, 2019.

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Clinical Articles

Hurdles imposed by payers and high drug costs present increasing barriers to technological and precision medicine advancements in cancer programs, according to a recent survey by the Association of Community Cancer Centers.

Technology Continues to Grow Despite Payment Hurdles, According to ACCC Survey

A series of exciting new findings and merit highlights have been reported in this month&rsquo;s issue of

. First, the combination of immune checkpoint inhibition with chimeric antigen receptor (CAR) T-cell therapy was used in relapsed B-cell acute lymphoblastic leukemia. Overall, 7 of 14 patients showed complete or partial responses to treatment with a PD-1 inhibitor plus CD19-directed CAR T-cell therapy, as reported by Shannon L. Maude, MD, PhD, of Children&rsquo;s Hospital of Philadelphia. She described these results at the 60th American Society of Hematology Annual Meeting and Exposition held from December 1 to 4, 2018. Although CAR T-cell therapy is effective for this patient population, relapses commonly occur within 12 months because of both CD19-positive and tumor-cell-escaping CD19-negative relapses. Maude and her team investigated the use of pembrolizumab (Keytruda) or nivolumab (Opdivo) in 14 patients, 6 of whom had poor persistence of response and 4 of whom had bulky extramedullary disease. Adverse events (AEs) were manageable and included mild cytokine release syndrome and fever, frequently seen with CAR T-cell responsiveness, and occasional pancreatitis, hypothyroidism, and other inflammatory conditions. There were 4 cases of grade 3/4 cytopenia. Although 2 patients had to discontinue the PD-1 inhibitor because of delayed AEs, in general, this combination was found to be feasible and showed promising clinical activity.

A watershed clinical trial was reported at the 2018 San Antonio Breast Cancer Symposium (SABCS) by Leisha A. Emens, MD, PhD, of the University of Pittsburgh Medical Center Hillman Cancer Center, detailing a biomarker subgroup analysis of the phase III IMpassion130 study in patients with metastatic or locally advanced, inoperable triplenegative breast cancer (TNBC). In the study, progression-free survival (PFS) and overall survival (OS) were improved with the addition of atezolizumab (Tecentriq) as a first-line treatment to nab-paclitaxel (Abraxane), but only in the subset of patients with PD-L1 expression &ge;1% in immune cells. Because of the large number of potentially eligible patients, these biomarker analyses greatly affect clinical practice and physicians&rsquo; decision making. Emens performed exploratory analyses of other biomarkers including PD-L1 expression on tumor cells, intratumoral CD8-positive T cells, as well as BRCA1/2 mutational status, demonstrating the importance of PD-L1 expression on immune cells and predicting clinical benefit from atezolizumab plus nab-paclitaxel. These data support the routine testing of PD-L1 immune cell status to help oncologists determine whether patients might benefit from atezolizumab plus nab-paclitaxel. Among the subgroup with PD-L1&ndash;negative immune cells, the median PFS was 5.6 months in both treatment arms. However, for those 41% of patients who had PD-L1 expressed on tumor-infiltrating lymphocytes, the median OS was 25 months in the atezolizumab/nab-paclitaxel chemotherapy group compared with 15.5 months in those who received nab-paclitaxel alone (HR, 0.62; 95% CI, 0.45-0.86; P = .0035). These results indicate that immunotherapy for TNBC is here and may be effectively combined with taxane-based chemotherapy, paving the way for novel and innovative regimens as well as supporting the use of biomarker studies, as Emens so elegantly presented.

Another promising finding at SABCS, with simultaneous publication in the New England Journal of Medicine, was of the phase III KATHERINE study using adjuvant ado-trastuzumab emtansine (Kadcyla). Treatment with ado-trastuzumab reduced invasive breast cancer recurrence or death by 50% compared with trastuzumab (Herceptin) in patients with HER2-positive early breast cancer who had residual disease after neoadjuvant therapy. These data were presented by Charles E. Geyer Jr, MD, of the Virginia Commonwealth University School of Medicine, who concluded that the results present a &ldquo;statistically significant and clinically meaningful improvement in invasive disease-free survival&rdquo; over standard-of-care trastuzumab alone (see page 33). This large trial enrolled patients after neoadjuvant chemotherapy containing a taxane alone or with anthracycline and at least 9 weeks of trastuzumab. With a roughly 1:1 randomization, the safety analysis indicated that the majority of AEs were grade 1/2, with milder symptoms. Grade 3 AEs or greater occurred in slightly more patients (25.7% vs 15.4%) with ado-trastuzumab, and AE-related discontinuations occurred in 18% of patients in the experimental arm versus 2.1% in the control arm. Given that ado-trastuzumab induced a 50% reduction in risk of recurrence versus trastuzumab, it is very unlikely that the antibody pertuzumab (Perjeta) would have that much benefit over trastuzumab as a current standard in such a high-risk popu- lation, with an impact on the most appropriate adjuvant therapy for those with residual disease after neoadjuvant chemotherapy.

Robert L. Ferris, MD, PhD, co-physician editor in chief of Targeted Therapies in Oncology, discusses exciting new findings and merit highlights reported in this month&#39;s issue.

Advances in Breast Cancer and Hematology Increasingly Rely on Immunotherapy

Presentations at the 60th American Society of Hematology (ASH) Annual Meeting & Exposition were dominated by advancements in the treatment of chronic lymphocytic leukemia (CLL). Searches for CLL among oral presentations and poster sessions yield 371 entries.

High on the list of discussions was the efficacy of standard-of-care ibrutinib (Imbruvica) and novel immunotherapy combination regimens.

&ldquo;This was a big year at ASH for targeted therapy,&rdquo; said Jennifer A. Woyach, MD, associate professor at The Ohio State University Comprehensive Cancer Center in Columbus, who presented her own research at the meeting. The paradigm for frontline therapy is moving away from chemotherapy to targeted agents given alone or in combination. &ldquo;Some of the biggest news this year [included] the results of 2 trials of frontline therapy showing superior efficacy of ibrutinib alone or with rituximab [Rituxan] versus chemoimmunotherapy,&rdquo; she said.

Woyach was also interested in updates on the combination targeted therapy trials and the extended follow-up from the MURANO trial of venetoclax (Venclexta) plus rituximab.

This study, along with trials of ibrutinib plus venetoclax with or without other immunotherapy agents, involved patients treated with novel targeted combination therapies. All these studies, however, have relatively limited follow-up, so updates at future meetings when the data have further matured will be of interest, she said.

Alliance A041202: Ibrutinib in Older, Untreated Patients With CLL

Woyach presented data from the phase III Alliance A041202 study, which she said was designed to investigate the optimal treatment for older patients with CLL.

The study compared the Bruton&rsquo;s tyrosine kinase (BTK) inhibitor ibrutinib as monotherapy and in combination with rituximab, as well as the combination of bendamustine and rituximab, for patients &ge;65 years with previously untreated CLL. Investigators found that ibrutinib alone or in combination with rituximab produced superior progression-free survival (PFS) versus bendamustine plus rituximab, but there was no significant difference between ibrutinib and ibrutinib plus rituximab.

The 24-month PFS rate was 87% (95% CI, 81%-92%) for ibrutinib monotherapy, 88% (95% CI, 81%-92%) for ibrutinib plus rituximab, and 74% (95% CI, 66%-80%) for bendamustine plus rituximab.

Results of the study showed no overall survival (OS) difference between the 2 ibrutinib arms, which investigators attributed to a short follow-up and a crossover study design. Patients who progressed on bendamustine plus rituximab were allowed to cross over to ibrutinib.

The results were not particularly surprising, Woyach said. &ldquo;From the initial data from PCYC-1102-CA [NCT01105247] and RESONATE-2 [NCT01722487], frontline ibrutinib did appear to be more effective than chemoimmunotherapy, but it remains very important to do these large studies to establish this,&rdquo; she said. In 2017, randomized phase II data presented at ASH comparing ibrutinib alone with the combination of ibrutinib and rituximab also did not show an advantage to adding rituximab,

but this was a smaller trial in a different group of patients.

Ibrutinib was granted an expanded approval in 2016 to include single-agent ibrutinib therapy as a valid frontline therapy option; the FDA based its decision on data from the RESONATE-2 trial, which compared ibrutinib with chlorambucil.

This trial is the first comparing ibrutinib with a commonly used and very effective chemotherapy regimen.

Woyach said that their findings suggest that ibrutinib monotherapy should be the efficacy standard against which to measure other drugs in CLL trials for older patients.

iLLUMINATE: Up-front Ibrutinib Plus Obinutuzumab in CLL/SLL

Results from the phase III iLLUMINATE trial (NCT02264574) showed that ibrutinib plus obinutuzumab (Gazyva) was an effective chemotherapy-free treatment regimen compared with the chemoimmunotherapy regimen chlorambucil and obinutuzumab in patients with treatment-naïve CLL or small lymphocytic lymphoma (SLL).

This study included a genomically defined high-risk CLL population, according to the investigators.

&ldquo;Similar to the Alliance trial, [results from] this study show that ibrutinib plus a CD20[-directed] antibodyin this case, obinutuzumab&mdash;is superior to chemoimmunotherapy,&rdquo; Woyach said.

The chemotherapy-free arm showed a 77% reduction in risk of disease progression or death for patients with CLL or SLL and an 85% reduction for patients with high-risk CLL compared with the chemoimmunotherapy arm. OS had not yet been reached in either study arm.

The minimal residual disease (MRD) analysis for the intention-to-treat population showed that 35% of patients had undetectable MRD on ibrutinib plus obinutuzumab in bone marrow and/or peripheral blood testing versus 25% of those in the chlorambucil plus obinutuzumab arm. In the high-risk population, 27% versus 15% of patients had undetectable MRD in the ibrutinib plus obinutuzumab and chlorambucil plus obinutuzumab arms, respectively.8

Based on the trial findings, the FDA granted a priority review designation in October 2018 to a supplemental new drug application for the front-line regimen of ibrutinib plus obinutuzumab in this patient population.

&ldquo;[Results from] this study do not show that ibrutinib plus obinutuzumab is better than ibrutinib alone, but [the data] are promising. In the absence of a head-to-head trial, it would be reasonable to use this regimen,&rdquo; she noted.

In January 2019, the FDA approved the combination of ibrutinib plus obinutuzumab for the treatment of patients with CLL/SLL in the first-line setting based on these trial data, making it the first chemotherapy-free regimen that includes an anti-CD20 antibody approved in the United States to treat this patient population.

ECOG-ACRIN Study E1912: Ibrutinib Plus Rituximab Versus FCR

The phase III ECOG-ACRIN study E1912 (NCT02048813) compared ibrutinib and rituximab with standard fludarabine, cyclophosphamide, and rituximab (FCR) chemoimmunotherapy in untreated patients &le;70 years.

The study found OS and PFS advantages for ibrutinib plus rituximab versus FCR.

This trial, as well as the Alliance and iLLUMI- NATE trials, was designed to span the entire population of patients with CLL and broadly compare chemoimmunotherapy with targeted therapy, said Woyach.

&ldquo;That was really unexpected to see a survival advantage, especially so early on,&rdquo; said Woyach. &ldquo;[Results from] iLLUMINATE, Alliance, and [E1912] show us that for most patients, a targeted therapy should be the frontline standard of care.&rdquo;

These agents are not perfect for all patients, Woyach added. &ldquo;In older patients, there are associated toxicities that make it unappealing to give ibrutinib to everybody for the rest of their lives, but certainly these trials establish ibrutinib alone or with antibodies as the standard of care from which we need to build on, to move the field forward. It also tells us, for patients with a higher-risk CLL, that chemoimmunotherapy as frontline therapy should not be the go-to.&rdquo;

The E1912 investigators noted in their abstract that the findings have immediate practice-changing implications, &ldquo;establishing ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL.&rdquo;

CLARITY: Ibrutinib Plus Venetoclax in R/R CLL

Findings from the phase II CLARITY study showed that combination ibrutinib plus venetoclax was tolerable in patients with relapsed/refractory CLL.

In 39% of patients, the combination induced MRD negativity in the bone marrow after 12 months.

More than 90% of patients achieved an objective response, with 54% in complete remission (CR) or CR with incomplete marrow recovery after 12 months of treatment.

This was one of 3 studies presented at ASH with this drug combination, said Woyach; the other studies were from The University of Texas MD Anderson Cancer Center and The Ohio State University.

&ldquo;Looking at them all together, they show that these combinations are extremely effective for CLLboth up front and in the relapsed/refractory setting. They have high rates of complete response, [meaning] MRD negative. These trials justify moving these regimens to phase III trials, to compare [them] to the standard of care,&rdquo; Woyach said.

Investigators on the CLARITY study said results showed deep remission in patients who are relapsed/refractory, and the drug combination can possibly be discontinued for those who achieve MRD eradication. In the trial, both ibrutinib and venetoclax were discontinued at 14 months if patients were MRD negative at 8 months; those who were MRD negative at 14 or 26 months discontinued therapy at month 26.

As single agents, ibrutinib and venetoclax are both successful in improving survival in CLL; however, they rarely induce MRD eradication asmonotherapies.

Seven-year efficacy results from the phase Ib/II PCYC-1102 trial and extension study (PCYC- 1103-CA; NCT01109069) examining ibrutinib monotherapy administered in both frontline and heavily pretreated populations with CLL and SLL showed sustained activity with the single-agent BTK inhibitor.

The median PFS and OS rates for the first-line setting had not yet been reached, whereas the 7-year PFS rate was 80% and the OS rate was 75%. For the relapsed/ refractory setting, the 7-year PFS rate was 32% and the OS rate was 52%. A median PFS of 51 months was observed, and the median OS had not yet been reached for this group.

Investigators suggested that the data were promising, showing that patients with remissions are living longer with this treatment. Starting ibrutinib treatment early for both CLL and SLL provides the best long-term efficacy, according to current data.

The retrospective phase I/II study (NCT01865617) induced an 80% response rate in patients with relapsed/refractory CLL with concurrent therapy with ibrutinib and JCAR014, a CD19-targeted chimeric antigen receptor (CAR) T-cell therapy.14,15 Investigators also found higher in vivo expansion of CD4-positive CAR T cells plus lower rates of severe toxicity. That included rates of grade &ge;3 cytokine release syndrome (CRS) compared with a similar group of patients receiving only JCAR014.

Rather than giving JCAR014 after patients progressed on ibrutinib, investigators hypothesized that giving ibrutinib during leukapheresis and lymphodepletion, as well as during CAR T-cell therapy, would benefit patients by preventing tumor flare upon withdrawal, improving CAR T-cell function, decreasing CRS and other CAR T-cell treatment toxicity, and moving disease from the lymph nodes and into the blood. The study compared these patients with a previous cohort whose ibrutinib administration ended before infusion of CAR T cells.

Investigators said the results were the most encouraging they had seen in human subjects for a targeted agent and CAR T-cell combination. The CAR T cells expanded robustly in both the concurrent ibrutinib and no-ibrutinib groups, but the ibrutinib group had no severe CRS cases during CAR T-cell treatment while still showing a high response.

&ldquo;There are preclinical data showing that ibrutinib&rsquo;s inhibitory effects on ITK [interleukin 2inducible T-cell kinase] can actually help with the expansion of T cells in vitrowith the initial expansion of T cells to allow the CAR to be generated in the first place,&rdquo; Woyach said.

Ibrutinib is an immunomodulatory agent for the same reasonit inhibits ITK and can normalize parts of the immune microenvironment. &ldquo;It is exciting and makes sense with the preclinical data and what we know about the effects of ibrutinib in normal cells,&rdquo; Woyach noted. The immune system of someone with CLL is so suppressed that adding ibrutinib, which modulates the immune system in a way to make it function more normally, can improve its function with CAR T cells, she said.

TRANSCEND-CLL-004: Liso-cel in Heavily Pretreated, High-Risk CLL

Patients who were previously treated with &ge;2 prior lines of therapy, including a BTK inhibitor, were treated with the investigational CD19- directed 4-1BB CAR T-cell product lisocabtagene maraleucel (liso-cel; JCAR017), administered in a defined CD4 and CD8 composition.

Results from the TRANSCEND-CLL-004 study (NCT03331198) found that liso-cel induced an 81.3% best overall response rate and a 43.8% CR rate.

Toxicities were seen as manageable, including CRS and neurologic events. Investigators noted a rapid achievement of CR and undetectable MRD in high-risk and standard-risk patients with CLL who previously received ibrutinib, the majority of whom also received venetoclax.

Investigators noted that in general, CR rates are low for CLL with continuous therapy required. Increasingly, MRD is seen as an important endpoint and as an independent predictor of improved survival. They said data from this study support continued development of single-dose liso-cel in the treatment of CLL.

Newer products are being developed and modifications are being made to CAR T-cell therapies and adjuvants such as ibrutinib. &ldquo;We are getting close to learning how best to use CAR with CLL. The CLL immune system is unique compared with what is seen in other hematologic diseases,&rdquo; in terms of making these products effective, said Woyach.

Results from a phase I/II study of the triplet regimen combining pembrolizumab (Keytruda) with novel agents umbralisib and ublituximab showed a 90% response rate in relapsed/ refractory CLL and a 50% response rate in patients with Richter transformation.

The median PFS was not reached for patients with CLL at 15.6 months, and the PFS rate at 12.0 months was 89%.

Investigators noted that clinical data show pembrolizumab is ineffective as monotherapy for relapsed or refractory CLL and has a 90% failure rate for Richter transformation, with a median OS of 2 months. They hypothesized that antiPD-1 therapy combinations will be successful in treating CLL and Richter transformation, especially in patients who are relapsed/refractory to ibrutinib, and suggested that PD-1 and PI3K blockade would be synergistic.

The triplet was well tolerated, with durable responses in patients who are BTK refractory and high risk. The study had 2 CRs in patients with Richter transformation. Patients did not have higher immune-mediated toxicities than would be expected with pembrolizumab or umbralisib alone. It is thought to be the first PD-1, anti-CD20, and PI3K&delta; inhibitor combination for this patient population.

The study is continuing to enroll patients with BTK-refractory CLL, as well as Richter transformation. Investigators are also amending the protocol to replace pembrolizumab with TG-1501, a novel antiPD-L1 agent.

&ldquo;This was an interesting regimen,&rdquo; said Woyach. &ldquo;We have not seen PD-1 inhibitors to be very effective prior to this in CLL.&rdquo; Although the study had only a few patients with Richter transformation, she said it was exciting to see some success.

Presentations at the 60th American Society of Hematology Annual Meeting &amp; Exposition were dominated by advancements in the treatment of chronic lymphocytic leukemia.

February 2 2019 | Targeted Therapies in Oncology

Technology Continues to Grow Despite Payment Hurdles, According to ACCC Survey

Advances in Breast Cancer and Hematology Increasingly Rely on Immunotherapy

Updates in Chronic Lymphocytic Leukemia: 60th ASH Annual Meeting