Long-Term Responders After Autologous Stem Cell Transplantation in Multiple Myeloma

Abstract

IntroductionMultiple myeloma (MM) is considered an incurable hematological neoplasm. For transplant-eligible patients, initial treatment includes an induction phase followed by an autologous stem cell transplantation (ASCT). Despite the introduction of several drugs in the past years, relapses still occur. Nevertheless, some patients achieve sustained responses after successful induction treatment and ASCT.MethodsWe retrospectively evaluated all patients diagnosed with MM in our institution who underwent induction treatment and ASCT between 1990 and 2015. The subset of patients who achieved a sustained response (any degree) for 5 or more years after ASCT without further treatment or signs of progression were distinguished as “long-term responders” (LTRs). In the non-LTR group, a cohort referred to as “prolonged responders” (PLRs) showed sustained response of at least 5 years after ASCT but eventually relapsed. We collected and analyzed clinical and laboratory data.ResultsTwo hundred and fifty patients were diagnosed with MM and received induction treatment and ASCT at our institution in the study period. Among them, 54 (21.6%) patients met the criteria for LTR. Some diagnostic features such as a younger age, female gender, ECOG performance status of 0, lower International Staging System (ISS) stage, lower bone marrow plasma cell infiltration, and lower serum levels of calcium, C-reactive protein, and lactate dehydrogenase (LDH) were found to be more prevalent in LTR. Female gender, an ECOG performance status of 0, a localized Durie-Salmon stage, an ISS of I–II, the absence of bone disease, and an LDH within normal range were also predictive of longer progression-free survival (PFS) and overall survival (OS) in the whole cohort. The depth of the response achieved after induction and ASCT as well as the administration of an IMID-based maintenance regimen may play a role in the differences observed on PFS between cohorts. A detectable M-protein with a monoclonal gammopathy of undetermined significance (MGUS)-like behavior was detected in one-third of LTR after ASCT. Although relapses continue to occur in patients who achieve a 5-year treatment-free period after ASCT, a plateau is observed in the survival curves at approximately 21 years of follow-up.

Multiple myeloma patients with a long remission after autologous hematopoietic stem cell transplantation

“…Previous studies have also reported on MM patients who achieved durable remission after treatment. A comparison of the results to several key studies that evaluated LTR in MM is presented in Table 4 [4][5][6]. Although there is no clear criteria to define LTR, all these studies including the present one, used a PFS of at least five to eight years as a cut-off between LTR and Fig.…”

“…Few reports have focused on MM patients with prolonged remissions after autoHCT; most of which had small numbers of patients and used varying methodologies. A single-center analysis from Spain identified 54 (22%) of 250 patients who were transplanted between 1990 and 2015 as patients with prolonged remission following autoHCT, defined as achieving a sustained response for more than 5 years after autoHCT [5]. A report from the Mayo Clinic identified 46 (9%) of 509 patients as exceptional responders after autoHCT, defined as having a PFS of at least eight years without any maintenance therapy [6].…”

A Report of a Symptomatic Progressive Myeloma during Pregnancy and Postpartum Period from Asymptomatic State

“…This may suggest a causal relationship between the evolution of myeloma and pregnancy progression and a role of modifications in hormonal and cytokine milieu during pregnancy. It could be argued that, in the case we are talking about, it has been four years since her autologous transplant therefore her myeloma may have naturally progressed—irrespective of pregnancy—as the median time to progression after autologous transplant is around 42 months [ 11 ]. However, it is equally important not to discard the effects of pregnancy on myeloma progression due to changes in hormonal and cytokine milieu.…”