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Rituximab after autologous HSCT improves EFS in mantle cell lymphoma
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SAN DIEGO — Patients with mantle cell lymphoma who underwent autologous hematopoietic stem cell transplantation experienced improved EFS with periodic rituximab maintenance therapy, according to findings of the phase 3 LyMa trial presented at the ASH Annual Meeting and Exposition.
Patients with mantle cell lymphoma usually respond to initial therapy but eventually relapse. Steven Le Gouill, MD, of the department of hematology at Nantes University Hospital in Nantes, France, and colleagues suggested that controlling or eradicating residual mantle cell lymphoma cells is critical to controlling the disease and reducing relapse.
The initial analysis included 299 patients (median age, 57 years; 79% men), 277 of whom completed four courses of rituximab (Rituxan; Genentech, Biogen), dexamethasone, high-dose cytarabine and salt platinum (R-DHAP) every 21 days. Those who failed to respond underwent treatment with four courses of R-CHOP-14 before autologous HSCT. Patients were conditioned for autologous HSCT with R-BEAM.
Researchers randomly assigned 240 patients who achieved response after autologous HSCT to rituximab (n = 120) or observation (n = 120). The rituximab group received one 375 mg/m2 infusion of the drug every 2 months for 3 years. EFS — defined as disease progression, relapse, death, severe infection or allergy to the study drug — served as the primary endpoint. Secondary endpoints included PFS and OS.
Median follow-up was 50.2 months from the time of randomization.
Overall, 4-year PFS was 67.8% (95% CI, 62.1-72.8) and 4-year OS was 78% (95% CI, 72.8-82.3).
The event rate was 20.8% in the rituximab arm compared with 39.2% in the observation arm. Four-year EFS was 78.9% (95% CI, 69.6-85.6) in the rituximab arm and 61.4% (95%CI, 51.3-69.9) in the observation arm (P = .0012). Rituximab yielded a significantly superior EFS (HR = 0.45; 95% CI, 0.28-0.74).
More patients assigned rituximab achieved 4-year PFS from randomization (82.2%; 95% CI, 73.2-88.4 vs. 64.6%; 95% CI, 54.6-73; P = .0005), as well as 4-year OS (88.7%; 95% CI, 80.7-93.5 vs. 81.4%; 95% CI, 72.3-87.7; P = .0413). Rituximab yielded a 60% lower chance of progression (HR = 0.4; 95% CI, 0.23-0.68) and a 50% reduction in mortality (HR = 0.5; 95% CI, 0.25-0.98).
“There were 16 progressions, 14 deaths and four severe infections in the rituximab group,” Le Gouill said. “Eighty-three patients completed maintenance.”
He added that in the observation group, there were 37 progressions, 25 deaths and four severe infections.
“As you can see, patients in the rituximab arm are doing much better than patients in the observation arm,” Le Gouill said.
Median PFS, OS and EFS from randomization had not been reached in either arm.
“Regarding the key question, we were able to demonstrate that rituximab maintenance can improve EFS, PFS and OS,” Le Gouill concluded. “One infusion every 2 months for 3 years should be recommended for transplanted mantle cell lymphoma patients.” – by Rob Volansky
Reference:
Le Gouill S, et al. Abstract 145. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Disclosure: Le Gouill reports no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.
Perspective
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Jeremy Abramson, MD
Maintenance rituximab (Rituxan; Genentech, Biogen) has demonstrated an OS benefit in older patients following R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone), when compared with maintenance interferon, but the role of maintenance rituximab in younger patients has been unanswered.
The LYSA and GOELAMS groups are addressing this question with a randomized trial of maintenance rituximab vs. observation following induction chemoimmunotherapy and autologous stem cell transplant in younger patients with mantle cell lymphoma. Two-hundred ninety participants were enrolled and received four cycles of R-DHAP (rituximab, dexamethasone, cytarabine and cisplatin). Those achieving complete or partial response underwent autologous stem cell transplant, whereas those without response received four cycles of R-CHOP, followed by autologous stem cell transplant if response was achieved. After R-DHAP, the overall response rate was 89%, with 77% of patients achieving a complete response. Two-hundred fifty-seven participants (89%) underwent autologous stem cell transplant consolidation, and ultimately 240 (83%) of patients underwent randomization to maintenance rituximab administered every 2 months for up to 3 years, or no further therapy.
Researchers found improved PFS, EFS and OS in patients receiving maintenance rituximab compared with no further therapy. The 4-year overall survival was 89% in maintenance rituximab patients compared with 83% in patients assigned to observation. These show outstanding efficacy of four cycles of R-DHAP induction therapy with a complete response rate of 77%, and most notably for an OS benefit for maintenance rituximab, which resulted in a 50% reduction in risk for death compared with observation alone.
Once peer-reviewed, these data would support routine use of maintenance rituximab for responding patients following upfront induction chemoimmunotherapy and autologous stem cell transplant consolidation for mantle cell lymphoma. Given the emergence of novel agents in mantle cell lymphoma such as ibrutinib (Imbruvica; Pharmacyclics, Janssen) and lenalidomide (Revlimid, Celgene), future efforts will focus on targeted combinations in maintenance, and chemotherapy-free induction strategies for younger and older patients.
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