Glofitamab with GemOx for diffuse large B-cell lymphoma

Abstract

1 Abramson and colleagues acknowledge that “due to the evolving global treatment standards for CAR [chimeric antigen receptor] T-cell therapies during the period of study enrolment, patients who were candidates for CAR T-cell therapy at study entry were not excluded from STARGLO”. For these patients at high risk of second-line failure, CAR T-cell therapy is approved irrespective of transplant eligibility and has shown curative potential, as evidenced by a plateau in the survival curves. 1,2 The presented Kaplan–Meier analyses illustrate outcomes for treatment groups but not for relevant risk factors within each group. PB reports research funding from Incyte, Merck Sharp & Dohme, Miltenyi Biotec, and Takeda Oncology; consulting fees from Bristol Myers Squibb/Celgene, Gilead Kite, Merck Sharp & Dohme, Miltenyi Biotec, Roche, and Takeda Oncology; honoraria for lectures or presentations from AstraZeneca, AbbVie, Bristol Myers Squibb/Celgene, Gilead Kite, Incyte, Merck Sharp & Dohme, Miltenyi Biomedicine, Roche, Beigene, and Takeda Oncology; and travel grants from Bristol Myers Squibb/Celgene, Gilead Kite, Incyte, Merck Sharp & Dohme, Miltenyi Biotec, Roche, and Takeda Oncology. BvT reports research funding from Esteve, Merck Sharp & Dohme, Novartis, and Takeda; consulting fees from AbbVie, Allogene, Amgen, Bristol Myers Squibb/Celgene, Cerus, Gilead Kite, Incyte, IQVIA, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Miltenyi, Novartis, Noscendo, Pentixapharm, Pfizer, Pierre Fabre, Qualworld, Regeneron, Roche, Serb, Sobi, and Takeda; honoraria for lectures or presentations from AbbVie, AstraZeneca, Bristol Myers Squibb/Celgene, Gilead Kite, Incyte, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Novartis, Roche, Serb, and Takeda; travel grants from AbbVie, AstraZeneca, Gilead Kite, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Pierre Fabre, Roche, Takeda, and Novartis; and participation on steering committees for Regeneron and Takeda.

We commend Jeremy S Abramson and colleagues for their study showing a relevant overall survival (OS) benefit for glofitamab plus gemcitabine and oxaliplatin (GemOx) over rituximab plus GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma (the STARGLO trial). ¹ Abramson and colleagues acknowledge that “due to the evolving global treatment standards for CAR [chimeric antigen receptor] T-cell therapies during the period of study enrolment, patients who were candidates for CAR T-cell therapy at study entry were not excluded from STARGLO”. ¹ Notably, 58% of patients in the STARGLO trial were treated for primary refractory diffuse large B-cell lymphoma. For these patients at high risk of second-line failure, CAR T-cell therapy is approved irrespective of transplant eligibility and has shown curative potential, as evidenced by a plateau in the survival curves. ^1,2 The presented Kaplan–Meier analyses illustrate outcomes for treatment groups but not for relevant risk factors within each group. However, the presented univariate analysis of risk factors suggests a highly relevant effect of refractoriness on survival outcomes with glofitamab plus GemOx: the median OS for patients with primary refractory diffuse large B-cell lymphoma is 10.2 months versus 25.5 months for all patients. We thus encourage Abramson and colleagues to provide treatment-specific Kaplan–Meier analyses of OS and progression-free survival for patients with primary refractory diffuse large B-cell lymphoma. Given the study's median follow-up of 20 months—twice the median OS in this cohort—such exploratory Kaplan–Meier analyses could yield valuable insights without additional follow-up and would allow estimation of survival outcomes beyond the median time-to-event and potential levels of plateauing. These analyses are urgently needed to help physicians and patients in search of a cure to make informed decisions about the treatment options for diffuse large B-cell lymphoma.

PB reports research funding from Incyte, Merck Sharp & Dohme, Miltenyi Biotec, and Takeda Oncology; consulting fees from Bristol Myers Squibb/Celgene, Gilead Kite, Merck Sharp & Dohme, Miltenyi Biotec, Roche, and Takeda Oncology; honoraria for lectures or presentations from AstraZeneca, AbbVie, Bristol Myers Squibb/Celgene, Gilead Kite, Incyte, Merck Sharp & Dohme, Miltenyi Biomedicine, Roche, Beigene, and Takeda Oncology; and travel grants from Bristol Myers Squibb/Celgene, Gilead Kite, Incyte, Merck Sharp & Dohme, Miltenyi Biotec, Roche, and Takeda Oncology. BvT reports research funding from Esteve, Merck Sharp & Dohme, Novartis, and Takeda; consulting fees from AbbVie, Allogene, Amgen, Bristol Myers Squibb/Celgene, Cerus, Gilead Kite, Incyte, IQVIA, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Miltenyi, Novartis, Noscendo, Pentixapharm, Pfizer, Pierre Fabre, Qualworld, Regeneron, Roche, Serb, Sobi, and Takeda; honoraria for lectures or presentations from AbbVie, AstraZeneca, Bristol Myers Squibb/Celgene, Gilead Kite, Incyte, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Novartis, Roche, Serb, and Takeda; travel grants from AbbVie, AstraZeneca, Gilead Kite, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Pierre Fabre, Roche, Takeda, and Novartis; and participation on steering committees for Regeneron and Takeda. RDJ reports payment or honoraria for lectures and presentations from AstraZeneca, BeOne, Janssen, and Roche; support for attending meetings and travel from Lilly, BeOne, and Janssen; and participation on an advisory board for BeOne.