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Sequential therapy with rituximab effective for CD20–positive posttransplant lymphoproliferative disorder
Rituximab plus CHOP consolidation was safe and effective in patients with CD20–positive posttransplant lymphoproliferative disorder, according to results of a prospective study.
“Most importantly, this prospective trial — the largest in posttransplant lymphoproliferative disorder to date — can demonstrate that CD20–positive posttransplant lymphoproliferative disorder in adults after solid organ transplantation is treatable and often curable with toxicity in the range reported for current standard treatments for diffuse large B-cell lymphoma,” Ralf U. Trappe, MD, professor of medicine in the department of internal medicine II, hematology and oncology at DIAKO Hospital Bremen in Germany, told HemOnc Today.
A previous study established sequential treatment with four cycles of rituximab (Rituxan; Genentech, Biogen) followed by four cycles of CHOP — or cyclophosphamide, doxorubicin, vincristine and prednisone — as the standard for management of posttransplant lymphoproliferative disorder. Researchers also identified response to four cycles of rituximab induction as a prognostic factor for OS after completion of sequential treatment.
“On this basis, we hypothesized that rituximab consolidation might be sufficient treatment for patients with complete response after rituximab induction,” the researchers wrote.
Trappe and colleagues evaluated data from 152 treatment-naive adult solid organ transplant recipients (median age, 56.4 years) with CD20–positive posttransplant lymphoproliferative disorder previously unresponsive to immunosuppression reduction. Patients received a treatment regimen of four weekly doses of 375 mg/m2 rituximab induction for 22 days.
At 50 days, patients were divided into high- and low-risk groups based on CT staging assessment of response. Complete responders, or low-risk patients, continued with four courses of rituximab consolidation every 21 days (n = 37; 375 mg/m2).
All other patients were considered high risk and received four courses of 375 mg/m2 rituximab plus 750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, 1.4 mg/m2 vincristine and 50 mg/m2 prednisone chemotherapy every 21 days (n = 111).
The primary endpoints were response rate in patients who completed therapy and response duration in patients who completed therapy and responded.
Among 126 patients, the overall response rate to risk-stratified sequential treatment after rituximab consolidation was 88% (95% CI, 81-93) and the complete response rate was 70% (95% CI, 61-77).
The median response duration was not reached, and the 3-year Kaplan-Meier estimate for response rate was 85% (95% CI, 74-90). Among the intention-to-treat patients (n = 152), the median time to progression also was not reached, with a 3-year Kaplan-Meier estimate of 75% (95% CI, 67%-82%).
The median OS was 6.6 years (95% CI, 5.5 years-7.6 years).
Fifty-seven of 91 patients (63%) experienced grade 3 or 4 leukopenia (95% CI, 52-72) and 52 of 151 patients (34%) experienced grade 3 or 4 infections (95% CI, 27-42). The frequency of treatment-related mortality was 8% (95% CI, 5-14).
Response to four doses of rituximab was a predictor for both time to progression and OS, regardless of treatment stratification (P < .001 for both).
The researchers note that the time to progression with risk-stratified sequential treatment in low-risk patients compared favorably with previous trials where only four cycles of rituximab were given to patients.
“Our simple algorithm of treatment stratification into rituximab or rituximab plus CHOP consolidation on the basis of response to rituximab induction allows all patients to be treated safely and effectively — 25% of them without chemotherapy,” Trappe said. “We thus provide an evidence-based standard therapy that takes into account the clinical diversity of posttransplant lymphoproliferative disorder as well as the increased risk for infections in transplant recipients.” – by Melinda Stevens
For more information:
Ralf U. Trappe, MD, can be reached at Department of Internal Medicine II: Hematology and Oncology, DIAKO Hospital Bremen, Gröpelinger Heerstr 406-408, 28239 Bremen, Germany; e-mail: rtrappe@gwdg.de.
Disclosure: Trappe reports owning stock in products by AbbVie, Bristol-Myers Squibb, Novartis and Roche; honoraria from Novo Nordisk and Roche; research funding to his institution from CSL Behring, Novartis and Roche; and other expenses paid for by Celgene, Gilead Sciences, Janssen Pharmaceuticals, LEO Pharma, Roche, Takeda Pharmaceuticals and TEVA Pharmaceutical Industries. Please see the full study for a list of all other researchers’ relevant financial disclosures.