ORLANDO – Patients with CD20-positive B-lineage acute lymphoblastic leukemia who received rituximab plus intensive chemotherapy had more durable remissions and better overall survival than did similar patients who received only chemotherapy, investigators reported at the annual meeting of the American Society of Hematology.
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In standard-risk patients, the addition of rituximab improved the continuous 5-year remission rate to 76%, compared with 42% for no rituximab. In addition, 90% of those who received rituximab had a molecular complete remission (MCR) after induction, vs. 59% of those who did not receive it, said Dr. Dieter Hoelzer of Johann Wolfgang Goethe University Hospitals in Frankfurt, Germany.
Among high-risk patients younger than 55 years, rituximab improved the survival rate after stem cell transplant from 41% to 69%, said Dr. Hoelzer, chair of the German Multicenter Trial for Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Adults (GMALL 07/2003).
The addition of rituximab was generally safe, and there were fewer treatment-related deaths in the larger cohort of patients who received rituximab. "In the rituximab arm, there is no increase of infections, but you need rigorous supportive therapy in those patients if you give rituximab and intensive chemo," Dr. Hoelzer commented.
The GMALL 07/2003 trial studied a highly complex intensive chemotherapy regimen involving cyclophosphamide, dexamethasone, vincristine, daunorubicin, doxorubicin, asparaginase, methotrexate, cytarabine, mercaptopurine, vindesine, etoposide, prednisolone, thioguanine, and teniposide, plus CNS and mediastinal irradiation. High-risk patients – those with white blood cell counts greater than 30,000/mcL and/or complete remission occurring later than 4 weeks – were offered stem cell transplantation with idarubicin, fludarabine, and cladribine with granulocyte colony–stimulating factor support.
Based on positive results with combined intensive chemotherapy and rituximab in the treatment of B-cell non-Hodgkin’s lymphoma, the protocol was amended in early 2004 to include rituximab for patients with CD20+ B-lineage acute lymphoblastic leukemia (ALL) (49% of the original GMALL 07/2003 cohort). The current study compared 82 CD20+ patients treated before the protocol was amended, and 181 treated afterward. Rituximab 375 mg/m2 was given on the day before the start of each induction, reinduction, and consolidation cycle, for a total of eight cycles.
In each cohort, more than 90% of patients had complete remissions after induction: 91% in the no-rituximab group and 94% in the rituximab arm. Among standard-risk patients younger than 55 years, 74% of those who received rituximab were still alive at longest follow-up of 6.5 years, compared with 58% of controls (no rituximab).
Rituximab was associated with a more rapid time to complete remission, with 57% of standard-risk patients who received it having an MCR by day 24, compared with 27% of controls. By week 16, 90% of patients on rituximab had an MCR, vs. 59% of controls.
Among 67 high-risk patients (43 in the rituximab arm and 24 in the no-rituximab arm), 81% of those on the CD20 inhibitor had a complete remission, compared with 88% of controls. Three patients on rituximab (7%) died during induction, compared with 1 (4%) of the controls. Stem cell transplant was possible in 25 patients on rituximab (71%) and in 19 controls (90%).
Among all high-risk patients, with or without transplant, rituximab was associated with a 55% 5-year survival rate, vs. 36% for controls, and among those who underwent transplant 5-year survival rates were 69% and 41%, respectively.
Grade 3 or 4 toxicities were generally similar in the two groups, with neutropenia occurring in 89% of patients in the rituximab arm after two induction courses, and 80% in the control arm. Fever occurred in 6% and 7%, and infection in 28% and 25%, respectively. There were three treatment-related deaths after stem cell transplant among patients on rituximab vs. four among controls.
The investigators plan to study rituximab maintenance in standard-risk patients, and whether additional rituximab given before and/or after stem cell transplant might provide additional benefits. In addition, they may examine whether rituximab has value in very-high-risk patients with B-lineage CD20+ ALL positive for the BCR-ABL fusion protein, Dr. Hoelzer said.
Dr. Hoelzer and his colleagues did not disclose the statistical significance of their findings, either in the published abstract or during the oral data presentation.
The study is sponsored by Johann Wolfgang Goethe University Hospitals in collaboration with Deutsche Krebshilfe e.V. and the German Federal Ministry of Education and Research, with partial funding from Hoffmann-La Roche. The authors had no conflict of interest disclosures. The study describes off-label use of rituximab.