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At this year's annual meeting of the American Society of Clinical Oncology (ASCO 2016), held June 3 to 7 in Chicago, investigators discussed the latest findings in cancer research. The editors of NEJM Journal Watch Oncology and Hematology were on hand to report highlights of the conference. Here, Associate Editor Michael E. Williams, MD, ScM, reviews key presentations on new treatments for patients with lymphoma and leukemia. All meeting abstracts can be viewed in the ASCO meeting library.
Most cases of classical Hodgkin lymphoma (cHL) overexpress PD-1 ligands and have shown high rates of response to PD-1 blockade. Younes and colleagues conducted a multicenter phase II trial involving 80 patients who had relapsed after autologous stem cell transplantation and after receiving brentuximab vedotin (BV) were treated with nivolumab once every 14 days (abstract 7535).
The overall response rate (ORR) was 66% (complete response [CR], 9%), and was 72% in BV nonresponders; 6 responding patients proceeded to a second stem cell transplantation. Progression-free survival (PFS) at 6 months was 77%. One treatment-related death occurred, 25% of patients had grade 3 or 4 toxicity, and 26% had grade 1 or 2 immune toxicities. Nivolumab was recently approved in the U.S. for this population of relapsed or refractory cHL.
Evens and colleagues conducted a randomized phase II trial to determine the effect of adding bortezomib to bendamustine-rituximab (BR) in 222 treatment-naive patients with previously untreated high-risk follicular lymphoma (defined as high tumor burden by GELF or FLIPI score 3 to 5; abstract 7507). Patients were randomized 1:2:2 to BR for 6 cycles followed by maintenance rituximab (MR) for 2 years versus BR plus bortezomib (BVR) for 6 cycles followed by MR for 2 years versus BR for 6 cycles followed by MR for 2 years plus lenalidomide for 1 year.
ORR was similar with induction BVR versus BR (91% and 90%, respectively). However, CR rates were improved with BVR versus BR (74% vs. 58%; P=0.016). Most patients in each treatment arm (86%) completed all 6 cycles of induction. Whether the higher complete response rate with BVR translates to longer-term benefit, and whether adding lenalidomide to MR improves outcomes, will require longer follow-up.
Maintenance rituximab is a standard of care following induction therapy with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone). Rummel and colleagues conducted a multicenter, prospective, randomized, phase II study to test the role of maintenance rituximab every 2 months for 2 years versus observation following 6 cycles of bendamustine-rituximab in 120 previously untreated mantle cell lymphoma patients who achieved a partial or complete response (abstract 7503).
At a median follow-up of 4.5 years, no differences were observed between the two arms in PFS or overall survival (OS). Caveats include the relatively small number of patients and the need for longer follow-up. Analysis of minimal residual disease (MRD) in bone marrow and peripheral blood following induction may better define those who would benefit from maintenance rituximab or consolidation strategies.
Circulating tumor DNA (ctDNA) in the plasma of diffuse large B-cell lymphoma (DLBCL) patients is a highly sensitive marker of disease activity after induction therapy. Kurtz and colleagues tested the dynamics of ctDNA response with outcomes in previously untreated DLBCL undergoing immuno-chemotherapy induction (abstract 7511).
A 2-log drop in ctDNA in the first 2 cycles of treatment in 33 patients correlated significantly with improved CR rate, PFS, and OS. In patients relapsing after initial CR, ctDNA reappearance preceded radiographic relapse by a median of 148 days, potentially allowing earlier intervention for poor-risk patients.
Jones and colleagues are conducting an ongoing, prospective, multicenter, phase II trial of the oral bcl-2 inhibitor venetoclax for poor-risk chronic lymphocytic leukemia patients who were relapsed after, refractory to, or intolerant of the B-cell receptor pathway inhibitors ibrutinib or idelalisib (abstract 7519).
In 48 evaluable patients, adverse features included del(17p) in 35%, bulky adenopathy in 24%, and unmutated IGHV in 83%. A stepped-up dosing schedule was utilized to avoid venetoclax-induced tumor lysis syndrome (TLS).
Of 38 patients previously treated with ibrutinib, 23 (61%) responded, including 3 who had a CR; only 1 had progressive disease. Of 10 patients previously treated with idelalisib, 5 (50%) responded. Grade 3 or 4 neutropenia occurred in 39%, and thrombocytopenia occurred in 22%; no clinical TLS was observed. Of 27 ibrutinib-relapsed patients observed at 24 weeks, 8 were MRD-negative.