February 2016, Vol. 5, No. 1

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Rituximab Boosts Chemotherapy Benefit in B-Cell Precursor ALL

ASH 2015, ASH Highlights

In patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the addition of rituximab to chemotherapy significantly improved event-free survival in a large European study.

“Adding rituximab to standard therapy should become a standard of care for these patients,” according to Sébastien Maury, MD, Hôpital Henri Mondor, Créteil, France.

The study population included patients with Philadelphia chromosome (Ph)-negative, CD20-positive BCP-ALL. The GRAALL-R 2005 phase 3 trial is the first randomized study to evaluate the role of rituximab in these patients.

“About one-third of patients with BCP-ALL have CD20-positive ALL, and in these patients the addition of rituximab is well tolerated, significantly improves event-free survival, and also prolongs overall survival in patients not receiving allogeneic stem cell transplant,” Maury said.

Up to 40% of patients with BCP-ALL express CD20, which confers a worse prognosis and is targeted by rituximab.

The multicenter, randomized GRAALL 2005 trial evaluated the potential benefit of adding rituximab to the pediatric-inspired GRAALL chemotherapy protocol in 220 patients with newly diagnosed CD20-positive Ph-negative BCP-ALL.

Event-Free Survival Significantly Improved

After a median follow-up of 30 months, patients treated with rituximab had a significantly lower cumulative incidence of relapse at 2 years (18%) versus controls (30.5%), who received only chemotherapy (P = .029). No significant differences were observed in nonrelapse mortality, which was 12% at 2 years in both arms.

The event-free survival rates at 2 years were 65% in the rituximab arm versus 52% in the control arm (hazard ratio [HR], 0.66; P = .038). Overall survival, however, was not significantly different: 71% with rituximab versus 64% without rituximab (HR, 0.70; P = .095).

The exception was in the subset of patients who did not undergo allogeneic stem cell transplantation in first complete remission. In this group, overall survival at 2 years was significantly prolonged with rituximab: 74% versus 63% with chemotherapy alone (HR, 0.55; P = .018). In patients not going to transplant, infection-related serious adverse events were similar.

Interestingly, fewer hypersensitivity reactions to asparaginase (a component of treatment) occurred in the rituximab arm, suggesting there could be a protective effect of rituximab via suppression of B cells producing antiasparaginase antibodies, Maury reported.

Results Called “Exciting”

In discussing the presentation at the ASH Plenary Session, Adele Fielding, MD, University College London, United Kingdom, noted that no novel agents have been introduced for the routine up-front treatment of Ph-negative ALL. Based on the findings from this study, she indicated, rituximab could become this new drug.

She said that questions remain as to the early and late toxicities for this combination, the types of patients most likely to benefit, the relationship between CD20 and response, and the correlation between minimal residual disease and response.

Press briefing moderator Robert Hromas, MD, University of Florida College of Medicine, Gainesville, commented that the benefit shown for rituximab “resolves a long-standing controversy” in this malignancy. “These results are exciting for those of us who treat leukemia,” he commented.

Colorectal Cancer - February 11, 2016

BRAF Mutation in Colorectal Cancer

Anita Turk, MD; Dustin Deming, MD
Division of Hematology and Oncology,Department of Medicine
University of Wisconsin-Madison School of Medicine and Public Health
and University of Wisconsin Carbone Cancer Center, Madison, WI

Advances in molecular pathology have allowed for the widespread use of sequencing technologies to improve our ability to better understand the biology of each individual patient’s cancer. This allows for the personalization of treatment strategies depending on the molecular profile of the cancer. In colorectal cancer (CRC), mutations in KRAS [ Read More ]

ASH 2015, ASH Highlights - February 12, 2016

Another Study Shows Benefit with a Pediatric Regimen in Young Adults with ALL

A pediatric regimen achieves superior outcomes compared with adult regimens in adolescents and young adults with acute lymphoblastic leukemia (ALL). Several studies have already shown this outcome, and a multicenter phase 2 study presented at the meeting adds further confirmatory evidence in support of this approach. The multicenter phase 2 [ Read More ]