Welcome to March/April, 2010 edition of OncoFacts. We are continuing our coverage of the important and potentially practice changing data from the 2009 Annual Meeting of the American Society of Hematology (ASH). This month, we will look at presentations concerning chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), and lymphoma.

Lymphomas

Abstracts 716 & 717
Two studies were presented by members of the German Hodgkin Study Group (GHSG). The first study (HD10) examined questions regarding the intensity of radiation therapy and chemotherapy in early-stage, favorable Hodgkin’s lymphoma. This study compared 2 cycles versus 4 cycles of doxorubicin, vinblastine, and dacarbazine (ABVD) and 20Gy involved field radiotherapy (IFRT) versus 30 GY IFRT. With a median follow-up of 79 months to 91 months, there was no significant difference in terms of overall survival (OS) between 2 and 4 cycles of ABVD and between 20 Gy and 30 Gy. The authors concluded that 2 cycles of ABVD followed by 20 Gy IFRT was the new GHSG standard of care for early stage Hodgkin’s lymphoma.

In a similar study (HD11), in early-stage unfavorable Hodgkin’s lymphoma, the German investigators attempted to answer the questions: 1) Can outcome be improved by intensifying chemotherapy, and 2) What is the best radiation dose? The trial compared 4 cycles of ABVD with 4 cycles of baseline bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) and 20 Gy IFRT with 30 Gy IFRT. They concluded that baseline BEACOPP is more effective than ABVD if the patients receive the lower dose of 20 Gy IFRT, but there is no difference if 30 Gy is administered. So both 4 cycles of baseline BEACOPP followed by 20 Gy IFRT and 4 cycles of ABVD followed by 30 Gy IFRT are acceptable as standards of care for the German Hodgkin Study Group.

Abstract 405
In 2007 at ASH, Mathias Rummel reported the results of a phase III study in advanced follicular, indolent, and mantle cell lymphomas comparing bendamustine-rituximab to R-CHOP. In that initial report from the StiL (Study Group Indolent Lymphomas), it was reported that the overall response rates (ORRs) for bendamustine-rituximab and R-CHOP were equivalent at 93% with the complete response (CR) rates for bendamustine-rituximab somewhat higher at 47% compared to 42% for R-CHOP. In addition, there were non-significant progression-free survival (PFS) advantages for indolent and mantle cell lymphomas with the use of bendamustine-rituximab. At the 2009 ASH meeting, Rummel updated these results in 513 evaluable patients. Overall response rates were similar at 93.8% for bendamustine-rituximab and 93.5% for R-CHOP. Complete response rate, however, was higher for bendamustine-rituximab at 40.1% versus 30.8% for R-CHOP. The median PFS, event-free survival (EFS), and time to next treatment (TTNT) were significantly longer for bendamustine-rituximab compared to R-CHOP.

ORR, overall response rate; CR, complete response; PFS, progression-free survival; EFS, event-free survival; TTNT, time to next treatment; AEs, adverse events

Grade 3-4 neutropenia and leucopenia were significantly more frequent with R-CHOP as were the number of infections, incidence of peripheral neuropathy, and episodes of stomatitis. The authors concluded that bendamustine-rituximab has the potential to become a new standard first-line therapy for follicular lymphoma, mantle cell lymphoma, and indolent lymphomas.

Abstract 407
Laurie Sehn from the British Columbia Cancer Agency reported the results of a phase II study in previously untreated, advanced follicular lymphoma. Bortezomib has been shown to have significant activity as a single agent in relapsed follicular lymphoma. This trial was designed to determine the safety, feasibility, and efficacy of adding bortezomib to the rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) regimen as front-line therapy for follicular lymphoma. Ninety-five patients were enrolled. Sixty-three percent had stage IV disease. Follicular Lymphoma International Prognostic Index (FLIPI) scores were low in 11%, intermediate in 43%, and high in 46%. Ninety-three percent completed all 8 planned cycles of therapy. Fifty-two achieved a CR/unconfirmed complete response (CRu), and 34% achieved a PR for an ORR of 86%. Progression-free survival at 18 months was 80%. Sixty-five percent of patients went on to receive maintenance rituximab. Rituximab-CVP plus bortezomib was well tolerated with 6.3% of patients experiencing grade-3 neurotoxicity, which was largely reversible. There was no grade 4 neurotoxicity.

Abstract 406
Richard Delarue of GELA reported the interim results of the LNH 03-6B study of R-CHOP-14 versus R-CHOP-21 in diffuse large B-cell lymphoma (DLBCL). Previous European trials in DLBCL have demonstrated several findings:

In this GELA trial, 202 patients (out of a total of 1080 patients accrued), ages 60-80 with advanced DLBCL were randomized to R-CHOP-14 versus R-CHOP-21 each for 8 cycles. Baseline characteristics were equal except for slightly increased incidences of stage III-IV, IPI >3, and age-adjusted International Prognostic Index (aaIPI) of 2-3 in the R-CHOP-14 arm. B-symptoms were more frequent in the R-CHOP-21 group. Median follow-up was 24 months. Event-free survival was the primary endpoint. Results reported demonstrated a non-significant trend towards increased PFS and EFS with R-CHOP-21 and somewhat less toxicity.

EFS, event-free survival; NS, not statistically significant; NR, not reported; PFS, progression-free survival; DFS, disease-free survival; OS, overall survival; CR, complete response; CRu, unconfirmed complete response; PR, partial response; RR, response rate

Toxicity generally was somewhat higher in the R-CHOP-14 group despite over 90% receiving prophylactic granulocyte colony-stimulating factor (G-CSF) compared to 60% in the R-CHOP-21 group. The authors concluded that the trial interim results favored the 21-day regimen in elderly patients with DLBCL with a trend towards greater efficacy and lower toxicity. Following the presentation, representatives of the German Lymphoma Study Group argued that their R-CHOP-14 regimen in RICOVER-60 had greater dose intensity than the GELA regimen and this might explain the lessened efficacy seen in the GELA trial.

All patients were younger than 65 years of age. Treatment regimens of the 167 patients were: R-CHOP = 29, R-CHOP followed by HDT/ASCT = 34, and hyper-CVAD = 104. There were no significant differences among the 3 groups in regards to International Prognostic Index (IPI) score, Charlson comorbidity index, bulky disease, or bone marrow involvement. Comparisons by pairs demonstrated that R-CHOP alone was inferior to both the R-CHOP followed by HDT/ASCT regimen and hyper-CVAD with regards to PFS and OS. There were no significant differences in PFS and OS between R-CHOP followed by HDT/ASCT and hyper-CVAD. Total unplanned hospital admissions and days were greatest with the hyper-CVAD regimen.

References
Engert A, Diehl V, Pluetschow A, et al. Two cycles of ABVD followed by involved field radiotherapy with 20 gray (Gy) is the new standard of care in the treatment of patients with early-stage Hodgkin lymphoma: Final analysis of the randomized German Hodgkin Study Group (GHSG) HD10. Blood. 2009;114(22). Abstract 716 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.

Borchmann P, Diehl V, Goergen H, et al. Combined modality treatment with intensified chemotherapy and dose-reduced involved field radiotherapy in patients with early unfavorable Hodgkin lymphoma (HL): Final analysis of the German Hodgkin Study Group (GHSG) HD11 Trial. Blood. 2009;114(22). Abstract 717 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.

Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab is superior in respect of progression free survival and CR rate when compared to CHOP plus rituximab as first-line treatment of patients with advanced follicular, indolent, and mantle cell lymphomas: Final results of a randomized phase III study of the StiL (Study Group Indolent Lymphomas, Germany). Blood. 2009;114(22). Abstract 405 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.

Sehn LH, Macdonald DA, Rubin S, et al. Bortezomib added to CVP-R is safe and effective for previously untreated advanced stage follicular lymphoma: A phase II study by the NCIC Clinical Trials Group. Blood. 2009;114(22). Abstract 407 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.

Delarue R, Tilly H, Salles G, et al. RCHOP14 compared to R-CHOP21 in elderly patients with diffuse large B-cell lymphoma: Results of the interim analysis of the LNH03-6B GELA Study. Blood. 2009;114(22). Abstract 406 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.

LaCasce A, Vandergrift JL, Rodriguez MA, et al. R-CHOP, followed by high dose therapy and autologous stem cell rescue (HDT/ASCR), and R-Hypercvad have equivalent progression-free survival and are superior to R_CHOP alone in younger patients with mantle cell lymphoma: A comparative effectiveness analysis from the National Comprehensive Cancer Network (NCCN) non-Hodgkin’s lymphoma outcomes database project. Blood. 2009;114(22). Abstract 403 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.

<< Chronic lymphocytic leukemia (CLL)

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