VAMP/ThaCyDex: Velcade® (Bortezomib), Adriamycin, Melphalan and Prednisone Alternating with Thalidomide, Cyclophosphamide and Dexametasone as a Salvage Regimen in Relapsed Multiple Myeloma Patients
Authors: Colado Enrique , Mateos Maria-Victoria , Moreno Maria-Jose , de Arriba Felipe , de la Rubia Javier , Lahuerta Juan José , Iniesta Pastora , Viguria Maria Cruz , Gonzalez Ana Pilar , García-Sanz Ramón , Olazabal Juan , Miguel Jesús F San 
Published: October 2019

Background: Bortezomib and Thalidomide have demonstrated to be effective in relapsed and refractory Multiple Myeloma (MM) patients, including those with adverse cytogenetics (CG). Moreover, Bortezomib and thalidomide-based combinations result attractive to improve efficacy, but toxicity could be increased. Based on this background, we have tested if an alternating regimen consisting on two highly effective schedules could overcome MM drug resistance without an increase in toxicity in relapsed/refractory MM patients.

Patients and Methods: Treatment schedule consisted on 6 alternating cycles of VAMP (Bortezomib 1,3mg/msq IV days 1,4,8 and 11; Melphalan, 9mg/msq po, days 1–4; Prednisone 60mg/msq po, days 1–4; and conventional or liposomal Adriamycin 40 or 30mg/msq respectively on day 1 of a 28 day cycle) alternating with ThaCyDex (Thalidomide 200mg/d po day 1–28; Cyclophosphamide 50mg/d po, days 1–28; and Dexametasone 40mg/d po, days 1–4). After 6 cycles, responding patients, received the previous schedule, every other month as consolidation therapy.

Results: From June 2007 until August 2008, 20 patients have been included, with a median age of 63 years (Range 48–81); 15 patients (75%) had previously received autologous stem cell transplantation. 6 patients (30%) had previously received Bortezomib-based therapy, and one patient (5%) had previously received IMID-based therapy. Efficacy and toxicity were evaluated on an intent-to-treat basis. After a median of 6 cycles, 20 patients were evaluable for response, 9 patients (42%) achieved immunofixation negative Complete Response (CR), 3 patients (16%) nCR, 9 patients (47%) partial response, which makes an ORR of 94,7%. In addition, 1 patient (5%) remained in stable disease and one patient died during induction therapy due to septic shock. Seven patients presented high risk cytogenetic abnormalities [t(4;14) and/or delRB], and CR was obtained in 3 of them (42%) plus one additional nCR in 1 patient (14%). Moreover, allogeneic stem cell transplantation was performed in two of these high risk patients, as they were effectively rescued by this salvage regimen. Two patients progressed during the consolidation treatment. Toxicity was manageable, being haematologic events the most frequently reported. 6 patients (30%) developed ≥G3 thrombocytopenia and 6 patients (30%) neutropenia. Infection ≥G3 occurred in 3 patients (16%). Despite the combination of two drugs with potential neurologic toxicity, the use of them in alternated schedule resulted in that only 3 patients (15%) developed Peripheral Polyneuropathy, none of them &gt;G2.

Conclusion: Preliminary results show that alternating VAMP/ThaCyDex is a highly effective salvage regimen in relapsed/refractory MM patients, including high risk subgroup with adverse cytogenetic abnomalities. Haematologic toxicity was the most frequent adverse event, while the incidence of Peripheral Polyneuropathy was low, despite the use of two neurotoxic drugs. This results indicate that the alternating approach allows the exposure to a large number of active drugs without increase in the toxicity. A second analysis will be performed in December 2008 and results will be updated.