2011 ASH Annual Meeting, December 10-13, San Diego, USA
Final results of the phase 3 VISTA trial: bortezomib-melphalan-prednisone (VMP) vs melphalan-prednisone (MP) for multiple myeloma
Dr Maria-Victoria Mateos – University Hospital of Salamanca, Spain
On behalf of the Spanish myeloma group, I will present during this ASH the results of the second analysis conducted in our randomised trial, conducted by the Spanish myeloma group in elderly untreated myeloma patients to evaluate the role of maintenance therapy with bortezomib plus thalidomide or prednisone in elderly untreated myeloma patients. This trial was started in 2005, 250 patients were included in the trial. They first received six induction cycles consisting of VMP – bortezomib melphalan plus prednisone or bortezomib plus thalidomide plus prednisone, but basically based on the weekly administration of bortezomib. Thereafter patients received maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone. The first results of this trial were already published in The Lancet and no significant differences were observed between both induction regimes. So here we wanted to evaluate if maintenance therapy is able to upgrade the response rate obtained during induction with an acceptable toxicity profile and also to evaluate the progression free and overall survival.
We included in this analysis 178 patients, bortezomib as maintenance therapy was given at conventional dose, 1.3mg/m2 on days one, four, eight and eleven, every three months for up to three years, plus 50mg of thalidomide or 50mg on alternate days of prednisone. Baseline characteristics of the patients were similar in both arms but in terms of efficacy in monofixation relative complete remission rate increased from 24% up to 42% during maintenance therapy. Also no significant differences were observed between both maintenance arms, VT or VP, there is a trend towards higher complete remission rates for patients who received bortezomib plus thalidomide. When we evaluated the response to maintenance according to the previous induction regime received, we didn’t find significant differences and always VT was slightly higher as compared with VP.
The second point to evaluate was toxicity profile – very important because we are dealing with elderly patients and they are receiving maintenance therapy. Toxicity profile was very, very acceptable, a very low frequency of grade 3/4 adverse events and I’d like to note that 8% and 3% of grade 3/4 peripheral neuropathy were observed in bortezomib plus thalidomide or bortezomib plus prednisone respectively. But the most important finding is that most of the patients weren’t really worse in peripheral neuropathy and in fact only one patient had emergent peripheral neuropathy during maintenance therapy. In terms of progression free survival, again no significant differences between both maintenance arms but a trend towards longer progression free survival for patients receiving bortezomib plus thalidomide, 39 months versus 34 months, without influence by the previous induction regime previously received. In terms of overall survival, again similar figures, a trend towards longer overall survival for patients receiving bortezomib plus thalidomide - median overall survival was not reached versus 60 months on VPR. I think this is the most relevant finding observed in this update of our trial.
My key message would be that maintenance therapy with these bortezomib based regimes in elderly patients clearly contributed to improve the overall response rate, most importantly, the quality of response and, at this time, clearly the progression free survival, not yet benefit in overall survival. The second important point is toxicity profile because, I repeat, we are dealing with elderly patients, fragile patients and it is very important to give them, to offer them, a maintenance therapy but with a good quality of life without significant adverse events. And the third important point is that all these results, I think, represent a significant platform for further optimisation of the treatment of elderly patients, changing, for example, thalidomide by lenalidomide, another immunomodulatory agent, more potent and even less toxic.
I think our group contributed more than the new developments, contributed to the optimisation of the treatment of elderly patients because we have now significant efficacy results obtained in randomised trials - VISTA trial, MPT versus MP trials, MMO15 trials, MPR versus MPR plus maintenance or MP alone. But now with all these results we have to try to optimise the treatment of elderly patients and it is very important to evaluate, when we have in front of us an elderly myeloma patient, the biological age more than the chronological age, their comorbidities, their disabilities in order to tailor the treatment according to these characteristics. And probably a subgroup of elderly patients can’t receive a full dose of the new drugs because if you administer full dose to these type of patients, discontinuation is going to be mandatory. So I think we have to try to tailor the treatment according to the characteristics of the patients and this is our principle objective with all these trials conducted in elderly myeloma patients.