Bendamustine Plus Rituximab Offers New Standard of Care for Treatment of NHL and Indolent Lymphoma

NEW ORLEANS-There was good news at ASH 2009 on promising treatments for indolent lymphoma and aggressive non-Hodgkin's lymphoma. Also, a separate poster presentation showed that even just one cycle of postremission therapy extended survival in elderly patients with acute myeloid leukemia.

Bendamustine/Rituximab for Indolent Lymphoma

Bendamustine (Treanda) plus rituximab (Rituxan) was better tolerated and improved progression-free survival (PFS) compared with standard CHOP plus rituximab (CHOP-R) as first-line therapy for indolent lymphoma in a multicenter, randomized, controlled trial conducted by the German Study Group on Indolent Lymphoma (StiL).

“This study is potentially practice-changing,” said Mathias J. Rummel, MD, head of the department of hematology at Hospital of the Justus-Liebig, University of Giessen in Giessen, Germany.

The study included 549 symptomatic patients (splenomegaly, pain, large tumor burden) enrolled at 82 centers, with a median age of 64 years. Patients were randomized to either bendamustine plus rituximab (B/R) or CHOP-R. Of these, 513 patients were evaluable for toxicity and efficacy. Histologies were distributed equally between B/R and CHOP-R:

B/R

• 55% had follicular lymphoma

• 18% had mantle cell lymphoma (MCL)

• 27% had other indolent lymphomas

CHOP-R

• 56% had follicular lymphoma

• 19% had MCL

• 24% had other indolent lymphomas

MCL is not considered indolent but was included because it is not curable with standard therapy, according to Dr. Rummel's group (abstract 405).

B/R caused significantly less hematologic toxicity (grades 3 and 4 leukocytopenia, neutropenia, and need for growth factor support with granulocyte colony-stimulating factor; P < .0001 for all comparisons). Alopecia did not occur in patients treated with bendamustine, whereas most patients treated with CHOP-R lost their hair. A much smaller percentage of patients in the B/R arm than in the CHOP-R arm experienced paresthesias, stomatitis, skin reactions, infectious complications, and sepsis.

Overall response rate (ORR) was similar for the two regimens: 92.7% for B/R and 91% for CHOP-R. Complete response (CR) occurred in more patients in the B/R arm than in the CHOP-R arm (39.6% vs 30%, respectively), and this translated to significantly better PFS at a median of 54.9 months for B/R vs 34.8 months for CHOP-R (P = .00012). Median follow up in this study thus far is 34 months.

Pixantrone for Aggressive NHL

Treatment with the novel investigational drug pixantrone (BBR2778) achieved significant increases in CR and ORR as well as a positive trend in overall survival (OS) compared with the use of other chemotherapy agents in patients with relapsed/refractory NHL, according to the phase III, randomized, open-label, multicenter EXTEND trial.

“An anthracycline with reduced cardiotoxicity that can be used for salvage therapy of aggressive NHL meets a significant unmet medical need,” noted lead investigator Ruth Pettengell, MD, of St. George's Hospital at the University of London.

The study enrolled 140 patients in whom at least one prior anthracycline-containing regimen and two prior treatment regimens for relapsed aggressive NHL had failed. Seventy patients were randomized to pixantrone (85 mg/m2 on days 1, 8, and 15 of a 28-day cycle for up to six cycles); 70 patients were randomized to a different single-agent comparator at the treating physician's discretion. Outside the U.S., these single-agents were vinorelbine (Navelbine), oxaliplatin (Eloxatin), ifosfamide, etoposide, and mitoxantrone. In the U.S., only gemcitabine (Gemzar) and rituximab were permitted. Patients in both groups were followed up to 18 months after the last treatment (abstract 1677).

After a minimum of nine months of follow up, CR and unconfirmed complete response (CR/CRu) was 25.7% for the pixantrone group vs 7% for the comparator arm (P = .005), and ORR was 40% vs 14.3% (P = .001). Median PFS after a minimum of nine months of follow up was 5.6 months vs 2.6 months, respectively (P = .002). Median OS was 10.2 months vs 6.9 months, respectively, a difference that was not statistically significant at a minimum of nine months of follow up. One-year survival was 45% for pixantrone vs 35% for the comparator arm.

Pixantrone was tolerable in these heavily pretreated patients. Serious cardiac adverse events occurred in 8.8% of the pixantrone group vs 4.5% of the comparator arm.

Lenalidomide in Aggressive NHL

Results of an international phase II study suggest that lenalidomide (Revlimid) should be studied in combination with other regimens in the treatment of the various subtypes of aggressive NHL and as maintenance therapy, according to Thomas E. Witzig, MD, from the Mayo Clinic College of Medicine in Rochester, Minn.

Lenalidomide is FDA-approved for the treatment of myelodysplastic syndromes and multiple myeloma. The trial was undertaken to confirm the safety and efficacy of single-agent lenalidomide in 217 patients with relapsed or refractory aggressive B-cell lymphoma after at least one prior therapy. Patients were required to have at least one measurable lesion
(> 2 cm). Treatment was with oral lenalidomide (25 mg/d on days 1 to 21 of a 28-day cycle) and was continued until disease progression or unacceptable toxicity (abstract 1714).

NHL subtypes included diffuse large B-cell lymphoma (n = 108), MCL (n = 57); follicular lymphoma-III (n = 19), and transformed lymphoma (n = 33). Median age of patients was 66 years.

According to the results, ORR was 35%, CR/CRu was 13%, partial response was 22%, and stable disease was 21%. Median PFS was 3.7 months, and median duration of response was 10.6 months. Responses were observed in all histologic subtypes and irrespective of prior therapies. The tolerability profile of lenalidomide was consistent with other studies of lenalidomide in hematologic malignancies. Reversible myelosuppression was the most common adverse effect.

Postremission Therapy in Older Adults With AML

Cytarabine-based postremission therapy (PRT) extended survival in elderly patients with AML in a single-institution study conducted at the Cleveland Clinic's Taussig Cancer Institute.

“Even after adjusting for patient disease and treatment factors that could influence PRT administration, older patients receiving at least one cycle of cytarabine-based PRT lived significantly longer than those who did not,” according to lead author Mikkael A. Sekeres, MD. He cited the need for a prospective, randomized, controlled trial to compare PRT with no PRT in elderly patients with AML, but indicated that in the absence of such a trial, PRT should be considered as part of intensive therapy.

The retrospective study was based on records of 215 patients: 81 received PRT and 134 did not. Median age was 68 years. Patients who received PRT were more likely to be younger and male; to have de novo AML, favorable- or intermediate-risk cytogenetics, and acute promyelocytic leukemia subtype of AML; and to have achieved a complete remission (abstract 1043).

Based on the study results, median disease-free survival was 0.45 years and 0.34 years for those receiving PRT and no PRT, respectively (P = .026), and median OS was 1.13 years and 0.69 years, respectively (P < .001).