Rituximab-based allogeneic transplant for chronic lymphocytic leukemia with comparison to historical experience

Mazyar Shadman, David G Maloney, Barry Storer, Brenda M Sandmaier, Thomas R Chauncey, Niels Smedegaard Andersen, Dietger Niederwieser, Judith Shizuru, Benedetto Bruno, Michael A Pulsipher, Richard T Maziarz, Edward D Agura, Parameswaran Hari, Amelia A Langston, Michael B Maris, Peter A McSweeney, Rainer Storb, Mohamed L Sorror, Mazyar Shadman, David G Maloney, Barry Storer, Brenda M Sandmaier, Thomas R Chauncey, Niels Smedegaard Andersen, Dietger Niederwieser, Judith Shizuru, Benedetto Bruno, Michael A Pulsipher, Richard T Maziarz, Edward D Agura, Parameswaran Hari, Amelia A Langston, Michael B Maris, Peter A McSweeney, Rainer Storb, Mohamed L Sorror

Abstract

Relapse of chronic lymphocytic leukemia (CLL) after allogeneic hematopoietic cell transplantation (HCT) remains a clinical challenge. We studied in a phase II trial whether the addition of peri-transplant rituximab would reduce the relapse risk compared with historical controls (n = 157). Patients (n = 55) received fludarabine and low-dose total body irradiation combined with rituximab on days -3, + 10, + 24, + 36. Relapse rate at 3 years was significantly lower among rituximab-treated patients versus controls (17% versus 31%; P = 0.04). Overall survival (OS), progression-free survival (PFS) and nonrelapse mortality (NRM) were statistically similar: (53% versus 50%; P = 0.8), (44% versus 42%; P = 0.63), and (38% versus 28%; P = 0.2), respectively. In multivariate analysis, rituximab treatment was associated with lower relapse rates both in the overall cohort [hazard ratio (HR): 0.34, P = 0.006] and in patients with high-risk cytogenetics (HR: 0.21, P = 0.0003). Patients with no comorbidities who received rituximab conditioning had an OS rate of 100% and 75% at 1 and 3 years, respectively, with no NRM. Peri-transplant rituximab reduced relapse rates regardless of high-risk cytogenetics. HCT is associated with minimal NRM in patients without comorbidities and is a viable option for patients with high-risk CLL. Clinical trial information: NCT00867529.

Conflict of interest statement

COMPETING INTERESTS

M. Shadman provided consultancy for Abbvie, Genentech, Astra Zeneca and Sound Biologics; has been on the advisory board for Abbvie, Genentech, Pharmacyclics, Astra Zeneca, ADC Therapeutics, Atara, and Verastem; and receives research funding from Mustang Biopharma, Pharmacyclics, Gilead, Genentech, TG Therapeutics, Bigene, Celgene, Acerta, Emergent, Sunesis and Merck. Otherwise, the authors have no other conflicts to declare.

Figures

Figure-1:. Kaplan–Meier curves for (A) overall survival,…
Figure-1:. Kaplan–Meier curves for (A) overall survival, (B) progression-free survival, (C) relapse, and (D) non-relapse mortality
comparing patients who were treated with rituximab-based conditioning on the phase-II clinical trial (red) and historical cohort patients (blue). P-values are by log-rank test.

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