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

We previously published a study where the treatment assignment of 162 newly diagnosed patients was based on the presence/ absence of an HLA-identical sibling (Bruno et al, N Engl J Med). First-line treatment plans included a cytoreductive autograft followed by a nonmyeloablative allograft (Tandem auto-allo) or a second melphalan-based autograft (Doubleauto). Primary endpoints were overall (OS) and event-free (EFS) survivals by intention-to-treat analysis. The 80 patients with a sibling donor were offered a Tandem auto-allo and the 82 without a Double-auto after high (140-200 mg/[m.sup.2] ) or intermediate dose melphalan (100 mg/[m.sup.2]). Importantly, neither induction or maintenance therapies with so-called "new drugs" were part of the treatment protocol. First statistical analyses were carried out at a median follow up of 45 (range 21-90) months, OS and EFS were significantly longer in patients with donors: 80 versus 54 months (p=0.01) and 35 versus 29 months (p=0.02). Median OS was not reached in the 58 (out of 60 enrolled, 97%) patients who completed Tandem auto-allo and was 58 months in the 46 (out of 59 enrolled, 78%) who completed high-dose doubleauto (p=0.03). Here, we report an update at a median follow up of 6 years: OS was not reached for the 80 patients with an HLA-identical sibling and was 52 months for those without (HR 0.53, CI 95% 0.34-0.81, p=0.004). EFS remained significantly longer in patients with HLA-identical siblings: 35 versus 29 months (HR: 0.63; 95% Cl: 0.44-0.89, p=0.009). Median OS was not reached in the 58 patients who completed Tandem auto-allo and was 64 months in the 46 who completed high-dose double-auto (HR 0.54, CI 95% 0.31-0.96, p=0.04). EFS was 37 and 33 months (HR 0.65, CI 95% 0.41-1.02, p=0.06). After a median follow-up of 75 months, Attal et al. (N Engl J Med) reported median OS of 48 and 58 months after one and two autologous transplants respectively. EFS of the entire cohort was 30 months. These data are consistent with our results (OS: 63 months; EFS: 33 months). We can safely conclude that Tandem auto-allo allow better clinical outcomes than standard Double-auto. We point out, however, that Double-auto is not universally regarded as "standard therapy" since the introduction of new agents such as bortezomib and lenalidomide. Thus, it is imperative to thoroughly explore their roles in the setting of allografting and compare clinical outcomes with those obtained with new drugs with/without autograting.