Significant Developments in Multiple Myeloma Treatment Highlights Oncology News Review

Top news of the week in cancer drug development.

Myeloma

BCMA-Directed CAR T-Cell Infusion Leads to Eradication of Myeloma

Genetically engineered T cells eradicated multiple myeloma cells in a single patient with advanced disease, suggesting the potential to cure the condition. In the small study, the patient initially had more than 90% multiple myeloma cells in his bone marrow that was reduced to 0% one month after an infusion of allogeneic T cells modified by an anti-B-cell maturation antigen (BCMA) CAR. See more at: http://www.onclive.com/conference-coverage/ash-2015/car-t-cell-infusion-leads-to-eradication-of-myeloma

Pembrolizumab Effective in Myeloma

The addition of pembrolizumab to lenalidomide and dexamethasone elicited responses in 76% of 17 patients with relapsed/refractory multiple myeloma. Among the 13 patients who responded to the combination therapy, 4 patients (24%) achieved a very good partial response and 9 patients (53%) exhibited a partial response. Additionally, 3 patients (18%) had stable disease, leaving only 1 patient whose disease progressed. The disease control rate, which measured any response plus stable disease lasting >12 weeks, was 88%. See more at: http://www.onclive.com/conference-coverage/ash-2015/pembrolizumab-combo-generates-high-response-rate-in-refractory-myeloma

Upfront Bortezomib Triplet Highly Effective in Myeloma

Induction therapy with a triplet of bortezomib, lenalidomide, and dexamethasone significantly improved progression-free survival and overall survival compared with lenalidomide and dexamethasone alone for patients with untreated multiple myeloma. In the study, labeled SWOG S0777, there was a 13-month improvement in PFS and a 29% reduction in the risk of death with the bortezomib triplet compared with lenalidomide and dexamethasone alone. Findings from the study suggest the triplet should be a new standard of care for untreated patients with multiple myeloma. See more at: http://www.onclive.com/conference-coverage/ash-2015/bortezomib-triplet-therapy-new-standard-of-care-for-untreated-multiple-myeloma

Newly Approved Ixazomib Triplet Highly Effective

An all orally administered regimen containing ixazomib, lenalidomide, and dexamethasone showed a 5.9-month improvement in progression-free survival compared with lenalidomide and dexamethasone alone for patients with relapsed/refractory multiple myeloma, according to data presented at the 2015 ASH Annual Meeting. In the phase III trial, labeled TOURMALINE-MM1, median PFS was 20.6 months with the ixazomib triplet compared with 14.7 months with lenalidomide and dexamethasone. The objective response rate was 78.3% with ixazomib versus 71.5% for the doublet therapy (P = .035). See more at: http://www.onclive.com/conference-coverage/ash-2015/oral-ixazomib-triplet-improves-pfs-in-myeloma

PFS, OS Sustained in Long-Term Elotuzumab Data

The combination of elotuzumab, lenalidomide, and dexamethasone showed sustained improvements in progression-free survival and overall survival for patients with relapsed/refractory multiple myeloma, according to a 3-year analysis of the ELOQUENT-2 trial. In updated data from the phase III study, the addition of the SLAMF7 antibody reduced the risk of progression or death by 27% and overall survival (OS) was improved by 4.1 months versus lenalidomide and dexamethasone alone. Additionally, the minimal incremental toxicity observed with elotuzumab remained consistent. See more at: http://www.onclive.com/conference-coverage/ash-2015/benefits-of-elotuzumab-sustained-in-3-year-myeloma-data#sthash.8Bejqs3m.dpuf

Carfilzomib Beats Bortezomib in Myeloma

Treatment with carfilzomib reduced the risk of progression or death by 47% compared with bortezomib for patients with relapsed multiple myeloma, according to findings from the phase III ENDEAVOR trial. In the study, the median progression-free survival with carfilzomib was 18.7 versus 9.4 months with bortezomib (HR, 0.53, P <.0001). Median overall survival was 24.3 months in the bortezomib arm but had not yet been reached in the carfilzomib group (HR, 0.79; P = .066). See more at: http://www.onclive.com/conference-coverage/ash-2015/carfilzomib-bests-bortezomib-across-multiple-myeloma-subgroups

Daratumumab Combo Effective, Safe for Myeloma

The addition of daratumumab to lenalidomide and dexamethasone generated responses in 81% of patients with relapsed or refractory multiple myeloma that were “rapid, deep, and durable” without introducing any new safety concerns. Responses included 11 patients who achieved a complete response (34%), 9 patients with a very good partial response (28%), and 6 patients with a partial response (19%). After 18 months, the progression-free survival rate was 72% and the overall survival rate was 90%. See more at: http://www.onclive.com/conference-coverage/ash-2015/daratumumab-combo-sparks-81-response-rate-in-myeloma

CLL

Frontline Ibrutinib Effective in CLL

Treatment with ibrutinib reduced the risk of death by 84% versus chlorambucil in treatment-naïve elderly patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, according to results from the phase III RESONATE-2 study. The results also showed a 2-year overall survival rate of 98% with ibrutinib. ORR was 86% with ibrutinib, with 4.4% of those being complete responses, versus 35.3% with chlorambucil, 1.5% of them complete responses. See more at: http://www.onclive.com/conference-coverage/ash-2015/frontline-ibrutinib-significantly-improves-survival-in-cll

Venetoclax Effective in High-Risk CLL

Venetoclax demonstrated an overall response rate of nearly 80% among patients with chronic lymphocytic leukemia harboring the chromosome 17p deletion, marking a promising new treatment option for patients with a poor prognosis. Overall, 79.4% of the 107 patients evaluated in the clinical trial responded to venetoclax monotherapy according to the independent review committee evaluation, including 8 patients (7.5%) with a complete response or a CR with incomplete marrow recovery. The results of the phase II trial have been submitted as part of new drug applications to the FDA and the European Medicines Agency, according to the pharmaceutical companies developing the drug. See more at: http://www.onclive.com/conference-coverage/ash-2015/venetoclax-sparks-high-response-rate-in-poor-risk-cll-subtype

Acalabrutinib Highly Effective in CLL

Acalabrutinib has demonstrated a 95% response rate and durable remissions with a favorable safety profile in a phase I/II study for patients with chronic lymphocytic leukemia. After a median 14.3-month follow-up, 57 of the 60 evaluable patients had achieved a partial response. Remissions were durable, with only 1 case of progression, irrespective of whether patients had high-risk CLL with a 17p deletion. The response rate among the 18 patients with the deletion was 100%. See more at: http://www.onclive.com/conference-coverage/ash-2015/next-generation-btk-inhibitor-taking-on-ibrutinib-in-cll

Idelalisib Effective With Bendamustine/Rituximab in CLL

Adding idelalisib to bendamustine and rituximab reduced the risk of progression or death by 67% compared with BR alone for patients with relapsed/refractory chronic lymphocytic leukemia. After 12 months of follow-up, the median progression-free survival with idelalisib was 23.1 months compared with 11.1 months for BR alone (HR, 0.33; P <.0001). Additionally, there was a 45% reduction in the risk of death with the addition of idelalisib to BR, although the median OS had not yet been reached in either arm (HR, 0.55; P = .008). See more at: http://www.onclive.com/conference-coverage/ash-2015/idelalisib-triplet-highly-effective-for-relapsed-refractory-cll

Acute Leukemia

CAR T-cells Impress in ALL

Impressive findings were presented for CD19 CAR T-cell therapies from Novartis and Kite Pharma for patients with acute lymphoblastic leukemia. In the first experience, CTL019 demonstrated a 93% CR rate in pediatric patients with relapsed/refractory ALL. After a median follow-up of 12 months, 79% of patients enrolled in the trial remained alive. The Kite CAR T-cell therapy showed a 100% CR rate in 9 patients with primary refractory ALL and for 5 patients with CNS ALL. All patients who achieved a CR also tested negative for minimal residual disease. See more at: http://www.onclive.com/conference-coverage/ash-2015/response-rates-near-100-for-car-t-cell-therapies-in-all

Midostaurin Improves Survival in AML

Patients with FLT3-mutated acute myeloid leukemia lived significantly longer when treated with the multikinase inhibitor midostaurin (PKC412) compared with placebo. Median overall survival with midostaurin was 74.7 versus 25.6 months in the placebo group (HR, 0.77). Event-free survival was over twice as long with midostaurin, at 8.0 versus 3.6 months. Once censored for stem cell transplant, midostaurin continued to show an improvement in OS. The 4-year censored OS rate with midostaurin was 63.8% versus 55.7% for placebo (HR, 0.75; P = .04). See more at: http://www.onclive.com/conference-coverage/ash-2015/midostaurin-shows-rare-survival-improvement-in-flt3-mutated-aml

Rituximab Effective in ALL

The addition of rituximab to chemotherapy improved outcomes in certain patients with acute lymphoblastic leukemia. The randomized trial showed that 2-year event-free survival increased from 52% with conventional therapy to 65% with the addition of rituximab among patients with newly diagnosed, CD20-positive Philadelphia chromosome-negative B-cell precursor ALL. Significantly more patients in the rituximab underwent stem-cell transplantation after complete response (34% vs 20%, P = .029). See more at: http://www.onclive.com/conference-coverage/ash-2015/adding-rituximab-to-chemo-boosts-survival-in-subgroup-of-all-patients

NHL

CAR T-cells Effective for Lymphoma

Updated findings from early stage clinical trials exploring CAR-modified T-cell therapies from Novartis and Juno continued to highlight the effectiveness of these approaches for patients with non-Hodgkin lymphoma. In the first study, CTL019 demonstrated an overall response rate of 73% and 47% in patients with follicular lymphoma and diffuse large B-cell lymphoma, respectively. In the second study, up to 82% of patients with NHL responded to JCAR014. Specifically in those with chronic lymphocytic leukemia, the ORR with JCAR014 plus fludarabine and cyclophosphamide lymphodepletion was 100%. The CR rate in this group was 57%. See more at: http://www.onclive.com/conference-coverage/ash-2015/high-response-rates-seen-with-car-t-cell-therapies-for-nhl