Here are several abstracts selected from the proceedings of the 2016 ASCO Annual Meeting, focusing on clinical trials on therapeutics in different types of leukemia, multiple myeloma, follicular lymphoma, and central nervous system (CNS) lymphoma. For full details of these study abstracts, visit meetinglibrary.asco.org.
Syed A. Abutalib, MD
Abstract 7000: Final results of a phase III randomized trial of CPX-351 vs conventional “7+3” regimen in older adults with newly diagnosed secondary acute myeloid leukemia (AML)1
Question Asked: Is overall survival using CPX-351 induction better than with conventional 7+3 therapy in older (aged 60–75 years) adults with secondary AML?
Abstract Conclusion: Yes. Treatment with CPX-351, a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio, resulted in superior overall survival (hazard ratio [HR] = 0.69; P = .005; median overall survival 9.56 vs 5.95 months), event-free survival (HR = 0.74; P = .021), and complete remission plus complete remission with incomplete peripheral blood count recovery response (47.7% vs 33.3%; P = .016). The 60-day mortality favored CPX-351 (13.7% vs 21.2%). Grade 3–5 adverse events were equal (92% vs 91%) and similar in frequency and severity in both arms. Similar numbers of patients were transplanted in both arms.
Abstract 7001: Treatment-free remission in patients with chronic myeloid leukemia (CML) in chronic phase treated with front-line nilotinib: Results from the ENESTFreedom study2
Question Asked: What is the treatment-free remission in specifically selected patients (n = 190) with CML in chronic phase following cessation of nilotinib (Tasigna)?
Abstract Conclusion: At week 48 of the treatment-free remission phase, 51.6% (95% confidence interval [CI]: 44.2%–58.9%) of the 190 patients were in major molecular response (see box) and had not reinitiated treatment. Of 86 patients who lost major molecular response and were restarted on nilotinib, 85 regained major molecular response (1 patient discontinued from the study [patient decision] without major molecular response 7.1 weeks after reinitiating nilotinib), and 76 regained molecular response 4.5.2 The median time to major molecular response and molecular response 4.5 among all patients who reinitiated nilotinib was 7.9 weeks and 13.1 weeks, respectively.2 No new safety signals were observed on treatment.
Abstract 7519: Venetoclax activity in chronic lymphocytic leukemia (CLL) patients who have relapsed after or are refractory to ibrutinib or idelalisib3
Question Asked: Is venetoclax (Venclexta) a viable option after failure of ibrutinib (Imbruvica) or idelalisib (Zydelig) monotherapy?
Abstract Conclusion: Yes. Fourteen of 22 ibrutinib-refractory patients and 3 of 5 idelalisib-refractory patients achieved response according to the International Workshop Group CLL criteria. Safety was consistent with prior reports with venetoclax. This is the first prospective study to demonstrate efficacy in this poor-prognosis population. Follow-up will assess the depth and duration of response in this ongoing study.
Abstract 8008: A phase I/II study of ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma4
Question Asked: What are the safety and preliminary efficacy data of this entirely oral regimen in relapsed/refractory multiple myeloma?
Abstract Conclusion: Twenty patients were evaluable for toxicity. Full-dose ixazomib (Ninlaro) with standard-dose pomalidomide (Pomalyst) and dexamethasone was well tolerated. Preliminary response rates are promising, given that more than 50% of patients were dual-refractory and early into the course of treatment.
Abstract LBA4: Phase III randomized controlled study of daratumumab [Darzalex], bortezomib [Velcade], and dexamethasone [DVd] vs bortezomib and dexamethasone [Vd] in patients with relapsed or refractory multiple myeloma: CASTOR study5
Question Asked: Is progression-free survival superior with DVd compared with Vd?
Abstract Conclusion: Yes. The overall response rate was 83% vs 63% (P < .0001), with very good partial response of 59% vs 29% (P < .0001) and complete remission rate of 19% vs 9% (P = .0012) for DVd vs Vd, respectively; median duration of response was not reached vs 7.9 months, respectively. DVd should be considered a new standard of care for relapsed/refractory multiple myeloma.
Abstract 7507: Effect of bortezomib on complete remission rate when added to bendamustine/rituximab in previously untreated high-risk follicular lymphoma: A randomized phase II trial of the ECOG-ACRIN Cancer Research Group (E2408)6
Question Asked: What is the added benefit of bortezomib on complete remission in combination with bendamustine/rituximab (Rituxan) in previously untreated high-risk follicular lymphoma?
Abstract Conclusion: A total of 222 patients (85 in the bortezomib and bendamustine/rituximab [BRV] group; 137 in the bendamustine/rituximab group) were randomized to the study. The overall response with BRV was 91% vs 90% with bendamustine/rituximab, whereas complete remission rates were 74% vs 58%, respectively (two-sided P = .016). The most common grade 3/4 toxicities (n = 241) for BRV vs bendamustine/rituximab were neutropenia (35% vs 30%), sensory neuropathy (12% vs 1%), thrombocytopenia (10% vs 5%), fatigue (6% vs7%), febrile neutropenia (3% vs 5%), and diarrhea (5% vs1%). Of note, 91% of grade 3 sensory neuropathy occurred with intravenous bortezomib (grade 3 sensory neuropathy incidence: 14% intravenous vs 4% subcutaneous, odds ratio = 3.7, P = .2). High-risk disease was defined as high tumor burden by GELF (Groupe d’Etude des Lymphomes Folliculaires) criteria and/or FLIPI (Follicualr Lymphoma International Prognostic Index) of between 3 and 5.
Abstract 2046: Phase I study of single-agent ibrutinib in recurrent/refractory primary and secondary CNS lymphoma7
Question Asked: Is the use of ibrutinib in heavily pretreated relapsed/refractory primary CNS lymphoma and secondary CNS lymphoma safe and tolerable?
Abstract Conclusion: A total of 10 patients were enrolled in the study, with 3 receiving 560 mg of ibrutinib and 7 receiving 840 mg of ibrutinib. Median age was 70 years (range, 21–80 years); 70% had primary CNS lymphoma and 30% had secondary CNS lymphoma. Six patients had parenchymal disease, three had isolated cerebrospinal fluid involvement, and one had both.
Treatment has been well tolerated, with two grade 4 toxicities (neutropenia and lymphopenia), which resolved after the drug was held. The most common toxicities observed were hyperglycemia, hypercholesterolemia, and thrombocytopenia.
After a median follow-up of 150 days, 9 patients were evaluated for response: 4 complete remissions (three in cerebrospinal fluid; one in the parenchyma), 3 partial remissions, and 2 progressive disease; the overall response rate was 78%. In a second treatment assessment, response has not been confirmed in two patients. Median time to first response was 28 days. Median progression-free survival was 6 months. Continued enrollment is ongoing, with a dose of 840 mg in an expansion cohort. ■
Disclosure: Dr. Abutalib reported no potential conflicts of interest.
1. Lancet JE, Uy GL, Cortes JE, et al: Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. 2016 ASCO Annual Meeting. Abstract 7000.
2. Hochhaus A, Masszi T, Giles FJ, et al: Treatment-free remission in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib: Results from the ENESTFreedom study. 2016 ASCO Annual Meeting. Abstract 7001.
5. Palumbo A, Chanan-Khan AAA, Weisel K, et al: Phase III randomized controlled study of daratumumab, bortezomib, and dexamethasone versus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma: CASTOR study. 2016 ASCO Annual Meeting. Abstract LBA4.
6. Evens AM, Hong F, Habermann TM, et al: Effect of bortezomib on complete remission rate when added to bendamustine-rituximab in previously untreated high-risk follicular lymphoma: A randomized phase II trial of the ECOG-ACRIN Cancer Research Group (E2408). 2016 ASCO Annual Meeting. Abstract 7507.