Addition of Thalidomide(Drug information on thalidomide) May Improve Outcomes in Elderly With MM
In multiple myeloma patients, the VMP combination (bortezomib, melphalan(Drug information on melphalan) [Alkeran], and prednisone(Drug information on prednisone)) has been shown to be superior to MP alone. For patients who relapse or become refractory to treatment, adding thalidomide to VMP can often induce a complete response. The large randomized study presented at ASCO by Palumbo et al (abstract 8515) further assessed the benefit of thalidomide when added to VMP earlier in the treatment course in treatment-naive patients. The drug was given with VMP and continued for 35 days. Patients received nine 5-week cycles.
At 3 years there were no significant differences among the VMP and VMPT groups in progression-free and overall survival, though numerically more patients were progression-free with the addition of thalidomide. There was, however, a highly significant difference in the rate of complete responses (35% with thalidomide vs 21% with VMP alone). Peripheral neuropathy rates were no higher with thalidomide, and the weekly infusions of bortezomib(Drug information on bortezomib) in this study resulted in less neuropathy than is seen with twice-weekly infusions. To determine clear benefits with thalidomide, we will need longer follow-up.
Similar Outcomes With R-ICE or R-DHAP in Relapsed DLBCL
In DLBCL patients with chemosensitive relapse, salvage chemotherapy followed by high-dose therapy and autologous stem cell transplantation is the standard of care. The CORAL study (abstract 8509), a randomized Intergroup trial, compared regimens that are often used—R-ICE (ifosfamide, carboplatin(Drug information on carboplatin), etoposide + rituximab(Drug information on rituximab)) and R-DHAP (dexamethasone, cytarabine(Drug information on cytarabine) [Ara-C], cisplatin(Drug information on cisplatin) [Platinol] + rituximab)—in DLBCL CD+ patients experiencing their first relapse or who were refractory to first–line therapy. Patients who responded received BEAM (carmustine [BiCNU], etoposide(Drug information on etoposide), cytarabine [Ara-C], melphalan) and ASCT (autologous stem-cell transplantation) and were then randomized to observation or rituximab for 1 year. The study found that both regimens had similar activity and mobilization ability, although there were fewer adverse events with R-ICE. The investigators evaluated for prognostic factors and found that prior rituximab exposure, relapse < 12 months, and secondary International Prognostic Index > 1 heralded lower response rates and shorter survival.
A correlative biomarker study is ongoing to better elucidate the population of patients with poor prognosis. A new profile of patients who relapse or become refractory after rituximab treatment is expected to come out of the results of the CORAL trial, and should inform the design of future studies with new agents. Meanwhile, these induction regimens appear to be equivalent, though R-ICE may be slightly less toxic and is my own preferred regimen.
A phase III trial comparing R-CHOP14 and R-CHOP21 for the treatment of patients with newly diagnosed diffuse large B-cell non-Hodgkin's lymphoma
D. Cunningham et al
Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in study SAKK 35/98
M.E. Ghielmini et al
Benefit of rituximab combined to ACVBP (R-ACVBP) over ACVBP in 209 poor-risk DLBCL patients treated with up-front consolidative autotransplantation: A GELA phase II trial (LNH 2003-3)
N. Mounier et al
A phase III study of VMPT versus VMP in newly diagnosed elderly myeloma patients
A.P. Palumbo et al
R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma followed by autologous stem cell transplantation: CORAL study
C. Gisselbrecht et al