The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.
Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International
Mantle cell lymphoma
The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.
By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.
“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.
The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.
In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.
The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.
Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.
With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.
The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.
MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.
In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.
The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.
SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.