A PETHEMA study of high-dose therapy/stem cell support (HDT), including tandem transplant, in primary refractory multiple myeloma (MM): Identification of two populations with different outcomes

Abstract

8021 Background: It has been claimed that patients with primary refractory myeloma benefit from early HDT. However, the reported series have 2 shortcomings: 1) patients with “unresponsive-progressive disease” vs those “non-responding-non progressing” were not analyzed separately and 2) some included patients had MR or even PR according to the EBMT criteria. Aim: Response and survival after early HDT in the two populations of truly primary refractory MM Methods: From Oct 1999 to Dec 2004, 829 patients with MM received 6 cycles of VBMCP/VBAD and at least one transplant. 79 of the 829 patients were refractory to VBMCP/VBAD. These resistant patients were scheduled to receive a tandem transplant, the first with Bu-12/MEL-140 or MEL-200 and the second “autologous” with CVB or “allo- RIC” (if donor available) with Fluda/MEL-140. Response and progression were defined by the EBMT criteria. Results: 32 of the 79 primary refractory patients had progressive disease under the initial chemotherapy while 47 were “unresponsive, non-progressive”. The prognostic features, including cytogenetics, were similar in both groups. 70% of the patients responded to the first HDT (CR/nCR 8%, PR 48%, MR 13%). 37 patients were given a second transplant (26 “auto”, 11 “allo”). 41% who received a second “auto” up-graded their response (CR 9%, PR 14%, MR 18%) while 42% who underwent “allo-RIC” increased their response (CR 28%, PR 14%). Median survival of the whole series was 3 years. Patients progressing while on therapy had a shorter survival than the “no-change” group (median 2 yrs vs not reached, p=0.00002). Finally, the 47 “non-responsive, non-progressors” patients had similar survival than the 718 with chemosensitive disease intensified with HDT. Conclusions: 1) HDT in patients with primary refractory MM results in a low CR rate, 2) patients progressing while on initial therapy have a short survival despite the intensive approach and 3) patients with “non-responding, non-progressive” disease have similar survival than chemosensitive patients. Whether this good outcome is due to the impact of HDT or to the natural history of a more indolent disease remains to be determined. No significant financial relationships to disclose.