Positive studies about brentuximab vedotin (Adcetris) in cutaneous T-cell lymphoma1 and rituximab (Rituxan) maintenance therapy in mantle cell lymphoma (MCL)2 were reported at the 2016 Annual Meeting of the American Society for Hematology (ASH).
Stephanie Lee, MD
“These abstracts each focus on approved agents and narrow disease states. The results of both studies will be clinically useful immediately,” said ASH secretary Stephanie Lee, MD, a hematologist at the University of Washington School of Medicine and the Fred Hutchinson Cancer Research Center in Seattle. Speaking at a pre-ASH Annual Meeting webinar, Dr. Lee selected these abstracts as actionable from a number of other abstracts that focus on “hot” topics, promising research, and phase II and III studies.
ALCANZA Trial
Cutaneous T-cell lymphoma is a relatively rare form of lymphoma that negatively impacts quality of life and has a poor prognosis when advanced. To date, no systemic therapy has proven superior to standard of care with either methotrexate or bexarotene (Targretin). Two phase II trials showed overall response rates of around 70% with single-agent brentuximab vedotin, leading to the phase III ALCANZA study presented at the 2016 ASH Annual Meeting.1
ALCANZA enrolled 128 previously treated patients with CD-30–expressing cutaneous T-cell lymphoma (97 with mycosis fungoides and 31 with primary cutaneous anaplastic large cell lymphoma). They were randomized to receive brentuximab vedotin at 1.8 mg/kg intravenously (IV) once every 3 weeks or physician’s choice (oral methotrexate at 5–50 mg once weekly or oral bexarotene at 300 mg/m2 once daily for up to 16 weeks [target dose]). Treatment was continued until disease progression or unacceptable toxicity.
At 17.5 months of follow-up, the study met its primary endpoint. The overall response rate that lasted at least 4 months was significantly higher for brentuximab vedotin than for physician’s choice of therapy: 56% vs 13%, respectively (P < .0001). Median progression-free survival was five times longer in the brentuximab-treated group: 16.7 months vs 3.5 months, which was highly significant in favor of brentuximab vedotin (P < .0001). Brentuximab vedotin achieved significantly greater reduction in skin symptoms compared with physician’s choice of therapy on the Skindex-29 symptom domain: –27.96 vs –8.62, respectively (P < .0001).
These data provide compelling evidence favoring brentuximab over physician’s choice of methotrexate or bexarotene in CD-30–expressing cutaneous T-cell lymphoma.— Youn H. Kim, MD
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“In this first report of a randomized phase III trial evaluating a new agent vs standard of care in cutaneous T-cell lymphoma, the clinical outcome of brentuximab was far superior to physician’s choice. These data provide compelling evidence favoring brentuximab over physician’s choice of methotrexate or bexarotene in CD-30–expressing cutaneous T-cell lymphoma,” said the lead study author Youn H. Kim, MD, of Stanford University School of Medicine, Palo Alto, California.
The percentage of serious adverse events was comparable in both arms (29% in each). However, the rate of peripheral neuropathy of any grade was much higher with brentuximab vedotin vs physician’s choice: 67% vs 6%. At the last follow-up, peripheral neuropathy was resolved or improved in 82% of patients in the brentuximab vedotin arm. There were more treatment discontinuations due to adverse events in the brentuximab vedotin arm: 24% vs 8%, respectively.
“The study showed improved response rates, progression-free survival, and symptom burden with brentuximab vs standard of care. More neuropathy was experienced in patients treated with brentuximab, but this improved over time. Brentuximab has significant advantages over the two other options used to treat cutaneous T-cell lymphoma,” Dr. Lee stated.
LyMa Trial
Mantle cell lymphoma accounts for about 6% of all non-Hodgkin lymphomas in adults. Although patients with mantle cell lymphoma commonly respond to initial therapy, inevitably they will relapse and receive retreatment with salvage therapy; and the relapse-free intervals shorten with each subsequent therapy.
For the first time, the LyMa trial demonstrates that rituximab maintenance after ASCT prolongs event-free survival, progression-free survival, and overall survival [in younger MCL patients].— Steven Le Gouill, MD, PhD
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“Indeed, there is an urgent need to control and/or eradicate residual MCL cells that are responsible for early and late relapses,” explained the lead study author Steven Le Gouill, MD, PhD, of Nantes University Hospital, France.
Rituximab maintenance therapy following rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) prolonged survival in elderly patients with mantle cell lymphoma. Until the present study, rituximab maintenance had not been studied after standard induction therapy with high-dose cytarabine followed by autologous stem cell transplantation (ASCT) in younger patients, he explained.
The phase III LyMa trial evaluated rituximab maintenance therapy (one infusion at 375 mg/m2 given every 2 months for 3 years) vs no maintenance therapy (observation) in 240 previously untreated younger patients with mantle cell lymphoma in response after induction therapy and autologous stem cell transplantation.2 The median age was 57 years (range, 27–65 years), and the median follow-up from the time of randomization was 50 months.
The primary endpoint was event-free survival from the time of randomization, with events defined as disease progression, relapse, death, or severe infection or allergy to rituximab. In an intent-to-treat analysis, median progression-free survival and overall survival were not reached in either arm at the time of the 2016 ASH Annual Meeting. Median 4-year progression-free survival and overall survival were superior in patients who received maintenance rituximab: 82.2% vs 64.6%, respectively (P = .0005), and 88.7% vs 81.4%, respectively (P = .0007).
Rituximab maintenance therapy reduced the risk of disease progression by 60% and the risk of death by 50% in an intent-to-treat analysis, and the results were similar in a per-protocol analysis.
“For the first time, the LyMa trial demonstrates that rituximab maintenance after ASCT prolongs event-free survival, progression-free survival, and overall survival. Thus, four courses of [dexamethasone, high-dose cytarabine, salt platinum] plus ASCT followed by rituximab maintenance as given in this trial is a new standard of care for younger MCL patients,” Dr. Le Gouill stated.
“The LyMa study provides good evidence that rituximab maintenance improves outcomes after ASCT in younger patients with MCL. Some hematologists are already doing this, and now we have phase III evidence for a survival advantage,” Dr. Lee commented. ■
Disclosure: Dr. Kim is an advisor or consultant to Kyowa Kirin Pharma, Horizon Pharma, Takeda, Eisai, Forty Seven Inc, Portola, and Seattle Genetics; she also has received research funding from Kyowa Kirin Pharma, miRagen, Merck, Soligenix, Eisai, Takeda, Neumedicine, Innate, Seattle Genetics, and Tetralogic. Dr. Le Gouill reported no potential conflicts of interest.
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