Long-term follow-up of a comparison of nonmyeloablative allografting with autografting for newly diagnosed myeloma

Abstract

Before the introduction of new drugs, we designed a trial where treatment of newly diagnosed myeloma patients was based on the presence or absence of HLAidentical siblings. First-line treatments included a cytoreductive autograft followed by a nonmyeloablative allograft or a second melphalan-based autograft. Here, we report long-term clinical outcomes and discuss them in the light of the recent remarkable advancements in the treatment of myeloma. After a median follow-up of 7 years, median overall survival (OS) was not reached (P ‫؍‬ .001) and event-free survival (EFS) was 2.8 years (P ‫؍‬ .005) for 80 patients with HLAidentical siblings and 4.25 and 2.4 years for 82 without, respectively. Median OS was not reached (P ‫؍‬ .02) and EFS was 39 months (P ‫؍‬ .02) in the 58 patients who received a nonmyeloablative allograft whereas OS was 5.3 years and EFS 33 months in the 46 who received 2 highdose melphalan autografts. Among patients who reached complete remission in these 2 cohorts, 53% and 19% are in continuous complete remission. Among relapsed patients rescued with "new drugs," median OS from the start of salvage therapy was not reached and was 1.7 (P ‫؍‬ .01) years, respectively. Allografting conferred a long-term survival and disease-free advantage over standard autografting in this comparative study. IntroductionAutologous transplantation has been regarded as the standard of care for young myeloma patients. 1 Recently, "new drugs" such as lenalidomide and bortezomib have prolonged survival. 2,3 Allografting has been considered the only potential cure. 4 However, the high transplant-related mortality (TRM) has limited its use. 5,6 After the observation that donor engraftment could be obtained after reduced-intensity purine analogbased or nonmyeloablative low-dose total body irradiation (TBI)-based conditionings, allografting has become more feasible with acceptable toxicity. [7][8][9] Combining an autograft with a nonmyeloablative conditioning and an allograft has lowered TRM to approximately 15% in myeloma. 10,11 However, role and timing of allografting remain to be determined and convincing evidence that an allograft should routinely be performed is lacking.We report the long-term results of a trial, designed before the introduction of "new drugs," where the treatment assignment of newly diagnosed patients under the age of 66 was based on the presence or absence of an HLA-identical sibling (ClinicalTrials. gov number, NCT00415987). 12 Methods Patients and treatmentsA total of 245 patients were consecutively diagnosed with stage IIA-IIIB myeloma from September 1998 to July 2004 at 5 Italian centers: San Giovanni Battista Hospital, Tosine; University of Udine, Udine; Santa Croce e Carle Hospital, Cuneo; Sant Antonio e Biagio Hospital, Alessandrio; IRCC, Candiole. Of 199 patients, 166 with at least 1 sibling were HLA-typed to search for a potential sibling donor. Written informed consent was obtained from all patients. The study was approved by the 5 Institutional Review Boards according to the Declaration o...

Reduced intensity-conditioned allogeneic stem cell transplantation for multiple myeloma relapsing or progressing after autologous transplantation: a study by the European Group for Blood and Marrow Transplantation

“…17,18,21 They are, however, worse than those for patients undergoing upfront RIC allo-SCT, which is not unexpected, given the prolonged disease history and more extensive prior therapies. [4][5][6][7][8][9][10][11][12] Although the relatively high NRM that we observed has to be taken into consideration, the data presented in this manuscript show that CMV-seronegative patients who have a CMV-seronegative donor have a substantially reduced NRM that translates into an encouraging 5-year survival of 440%. Considering that almost half (44.6%) of the patients in this study had undergone two or more prior autografts, our findings provide support to the notion that RIC allo-SCT can be an effective treatment option for some heavily pretreated patients.…”

“…27 However, previously published studies investigating allo-SCT in MM have not analysed the impact of CMV serostatus on outcome. [5][6][7][8][9][10][11]22,28,29 Primary infection or re-activation can occur in CMV-seropositive recipients and recipients of grafts from seropositive donors. The availability of sensitive monitoring methods for the detection of CMV reactivation, combined with pre-emptive anti-CMV therapy, Abbreviations: Auto-SCT ¼ autologous SCT; CI ¼ confidence interval; NRM ¼ non-relapse mortality; RIC allo-SCT ¼ reduced intensity-conditioned allo-SCT.…”

“…3 Over the last decade, a number of studies investigated up-front reduced intensity-conditioned (RIC) allo-SCT and reported substantially lower NRM rates compared with MA allo-SCT. [4][5][6][7][8][9][10][11][12][13] Whereas some of these studies reported better longterm outcomes with RIC allo-SCT compared with tandem autologous hematopoietic SCT (auto-SCT), others failed to demonstrate a benefit of up-front RIC allo-SCT. Therefore, there is widespread reluctance to offer patients' up-front allo-SCT, which is at least partly due to prolonged remissions that can be achieved following induction and/or maintenance therapy with novel agents.…”

Allogeneic stem cell transplantation for multiple myeloma: is there a future?

“…With a median follow-up of 7 years, the median OS was not reached (P = 0.02) and PFS was 39 months (P = 0.02) in the 58 patients who received an allo-SCT, whereas OS was 5.3 years and EFS 33 months in the 46 who received tandem ASCT. 32 In those achieving CR after allotransplant, 53% were in continuous complete remission compared with 19% for CR following tandem ASCT. This was the first randomized study that showed an advantage for allo-SCT over ASCT in MM and indicated that CR achieved after allotransplant was durable with a plateau in Abbreviations: Bu = busulfan; cGVHD = chronic GVHD; Cy = cyclophosphamide; EBMT = European Bone Marrow Transplantation; HOVON-24 = HaematoOncology Foundation for Adults in the Netherlands-24; m = months; Mel = melphalan; N/R = not reported; OS = overall survival; TRM = treatment-related mortality; y = years.…”

Isolated orbital relapse of multiple myeloma in a patient with severe chronic GVHD after allogeneic hematopoietic SCT

“…However, relapse of multiple myeloma is still a major concern after alloHSCT. 1,2 Whilst ocular involvement in chronic GVHD (cGVHD) is a frequent complication after alloHSCT, 3 ocular involvement by multiple myeloma is rare. 4 Here, we report a case of a 42-year-old male patient who presented with isolated orbital relapse of multiple myeloma during treatment of severe ocular cGVHD.…”