High Response Rate After 4 Courses of R-DHAP In Untreated Mantle Cell Lymphoma (MCL) Patients In the Ongoing Phase III Randomized GOELAMS and GELA LyMa Trial

The LyMa trial is established as a randomized, open-label, phase III study, to evaluate the efficacy of rituximab maintenance after autologous stem-cell transplantation (ASCT) in untreated mantle cell lymphoma (MCL) patients aged between 18 and 65 years old. The LyMa trial opened in September 2008. As of July 2010, 114 patients have been included. As in many other lymphoma entities, R-CHOP is still considered a standard of care for upfront MCL patients before ASCT. However, only 30–40% of MCL patients reach CR/CRu after R-CHOP. Since the response status (CR vs PR) before ASCT is associated with a better outcome it is important to find new alternative induction chemotherapy regimen. Growing evidences suggest that high-dose aracytine (HA) could be a major drug in MCL and should not be considered only at relapse. Several groups have highlighted a good response rate after upfront HA. More than 80% of the patients reach CR/CRu after intensive hyperCVAD/MTX regimen. The MCL2 trial from the Nordic group and the GELA trials have also demonstrated that higher response rates are achievable by alternating HA and R-CHOP. Therefore, the LyMa trial was designed to use 4 courses of R-DHAP (Rituximab 375mg/m² D1; Dexamethasone 40mg D1-4; High-dose Aracytine 2×2 g/m2 D2 and Cisplatin 100 mg/m² D1 but the choice of platinum salt was left at the discretion of local investigator) as induction therapy followed by ASCT using R-BEAM for newly diagnosed MCL patients. According to the design of the trial, only R-DHAP refractory patients (defined as a tumor burden reduction lower than 75% or progression) are eligible for R-CHOP prior ASCT.

The present analysis was performed in july 2010 and aims to evaluate prospectively the response rate after 4 courses of R-DHAP. All patients included before January 2010 (n=64) were eligible for the purpose of this analysis.

Median age is 57 years old (range, 30–65) and 53 (83%) patients are males. At time of diagnosis, 49 patients presented with Ann Arbor stage IV disease. All biopsies were centrally reviewed by pathologist experts from the GOELAMS and GELA groups. MCL diagnosis was confirmed in all reviewed cases. Eleven patients had a blastoid variant.

One patient withdraws is informed consent prior the start of the first cycle of R-DHAP. This patient has been excluded from the present analysis. All the other patients (n=63) have received at least one course of R-DHAP. Over the four courses of R-DHAP, 15, 24, 29 and 33 patients received another platinum salt than cisplatin. Four courses of R-DHAP were administered to 58 patients. For the remaining 5 patients, treatment was stopped for toxicity reason (n=3) or disease evolution (n=2). The two patients who progressed while on therapy received R-CHOP but both did not responded and died. Stem-cells were collected after more than 2 cytapheresis in only 4 cases. To date, fifty-three patients (84%) out of 63 underwent ASCT.

in an intention to treat analysis, the ORR after 4 courses of R-DHAP is 92% including 32 patients who reached CR and 20 patients who reached CRu according to Cheson criteria (JCO 1999). Taken together, the CR/CRu rate after 4 courses of R-DHAP is 82.5%.

R-DHAP alone is feasible with limited toxicity. This result of the ongoing LyMa trial confirms the major impact of HA in MCL untreated patients showing CR/CRu rates that are superior to those usually obtained with R-CHOP alone or alternating protocols such as R-CHOP/R-DHAP. FDG-PET analysis and response at the molecular level after 4 RDHAP courses have also been analyzed.

Off Label Use: velcade is of label in France for the treatment of mantle cell lymphoma. Tilly:Amgen: Honoraria.