Autologous stem cell transplantation (auto-SCT) has been the standard of care in eligible newly diagnosed multiple myeloma (MM) patients. Outcomes of patients with MM have improved significantly due to the advent of several novel drugs. Upfront use of these drugs in induction therapy has significantly increased the rate and depth of responses that have translated into longer remission and survival. This has now raised a debate regarding the role and relevance of auto-SCT in the management of myeloma. However, clinical trials have confirmed the utility of auto-SCT even in the era of novel drugs. Tandem auto-SCT followed by maintenance has shown a progression-free survival (PFS) benefit in high-risk MM, and hence can be considered in young and fit patients with high-risk disease. Auto-SCT has the advantages of resetting the bone marrow microenvironment, short-lived toxicity compared to the long-term physical and financial toxicities of continued chemotherapy in the absence of SCT, very low transplant-related mortality (TRM) in high volume centers, and providing longer disease-free survival when followed by maintenance therapy. Allogeneic SCT is one potentially curative option for MM, albeit with an increased risk of death due to high TRM. Strategies to modulate the graft-versus-host disease (GVHD) while maintaining or improving the graft-versus-myeloma (GVM) effect could place allogeneic SCT back in the treatment armamentarium of MM.

Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as a GVHD prophylaxis. However, there is variability in the serum concentrations of TAC, and little is known on the impact of early TAC levels on aGVHD. We retrospectively analyzed 673 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002 and 2016. Week 1 TAC was associated with a lower risk of aGVHD II–IV at TAC level ≥10.15 ng/mL (p = 0.03) compared to the lowest quartile. The cumulative incidence of relapse at 1, 3 and 5 years was 33%, 38% and 41%, respectively. TAC levels at week 2, ≥11.55 ng/mL, were associated with an increased risk of relapse (p = 0.01) compared to the lowest quartile. Subset analysis with acute myeloid leukemia and myelodysplastic syndrome patients showed significantly reduced aGVHD with TAC level ≥10.15 ng/mL at week 1 and a higher risk of relapse associated with week 2 TAC level ≥11.55 ng/mL (p = 0.02). Hence, achieving ≥10 ng/mL during the first week of HCT may mitigate the risk of aGVHD. However, levels (>11 ng/mL) beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse.

Introduction: Despite rapid advances in myeloma treatment with the development of new drugs, curative therapies remain elusive. Relapsed/refractory disease related to progressive dysregulation of immune system and acquired genetic abnormalities continues to be a major obstacle in achieving cure. Immune-based therapy harnessing the host defense mechanism of natural killer (NK) cells is a promising avenue in the treatment of myeloma. Areas covered: Here, we discuss the biology and cytotoxic activity of NK cells and the potential role of these innate immune cells in defense against cancer and specifically multiple myeloma. We also discuss the role of NK cells in the anti-myeloma effects of autologous and allogeneic stem cell transplantation, various novel drugs, and treatment modalities such as chimeric antigen receptor therapy. Immune evasion, either directly or indirectly involving NK cell dysfunction, may be a key and under-recognized mechanism in myeloma progression. We reviewed extensive literature identified using the keywords immunotherapy, natural killer cells, and multiple myeloma. Expert opinion: Novel treatment approaches in myeloma utilizing the immunomodulatory and cytotoxic properties of NK cells to eradicate resistant and quiescent clones could pave the way for potentially curative interventions.

Multiple myeloma (MM) represents 1.8% of all new cancer cases in the U.S. While not curable, advances in treatment, including autologous stem cell transplant (ASCT) and maintenance therapy, have dramatically improved progression-free survival (PFS) and overall survival (OS). We performed a retrospective survival analysis on newly diagnosed MM (NDMM) patients receiving ASCT from 1992–2016 at the Ohio State University. A total of 1001 consecutive NDMM patients were eligible. Patients were split into five groups based on historic changes in novel agents for the treatment of MM. Across the years (1992–2016), there was a statistically significant improvement in both PFS (p < 0.01) and OS (p < 0.01). Significant improvements in both PFS and OS were seen in patients ≤65 years (p < 0.001 and p = 0.002) and >65 years old (p < 0.001 and p = 0.001), respectively. Improved PFS and OS were seen in both standard-risk (p < 0.001 and p < 0.001) and high-risk patients (p < 0.001 and p = 0.019). The post-transplant response showed statistically significant improvement across the years (p < 0.01). Survival rates for NDMM patients have significantly improved primarily due to the inclusion of novel therapies and post-ASCT maintenance.

Background: Autologous stem cell transplantation (ASCT) remains an effective treatment option for many patients with systemic light chain (AL) amyloidosis. While maintenance post ASCT in multiple myeloma is now standard, the decision to utilize maintenance in AL amyloidosis remains largely unexplored. The present study aims to determine the prognostic significance of utilizing maintenance therapy following ASCT and assess the impact of fluorescent in situ hybridization (FISH) abnormalities, bone marrow plasma cell burden (BMPC), and degree of organ involvement on this decision. Methods and results: This is a retrospective analysis of fifty AL amyloidosis patients who underwent ASCT at The Ohio State University. Twenty-eight patients received maintenance and twenty-two did not. Kaplan–Meier survival analysis was used to compare the effect of maintenance therapy with no significant difference in PFS (p = 0.66) and OS (p = 0.32) between the two groups. There was no difference in survival based on maintenance when further categorized by FISH, PFS (p = 0.15), and OS (p = 0.65); BMPC ≥ 10%, PFS (p = 0.49), and OS (p = 0.32); or with 2 or more organs involved, PFS (p = 0.34) and OS (p = 0.80). Conclusion: Maintenance therapy post ASCT did not impact PFS or OS when categorized by FISH abnormalities, increasing BMPC, or ≥2 organs involved in AL amyloidosis patients.

Allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical (haplo) donor has emerged as a suitable alternative in the absence of a matched donor. However, haplo-HCT patients have a higher risk of graft-versus-host disease (GVHD). Hence, bone marrow (BM) stem cell source and post-transplant cyclophosphamide (PTCy) have been routinely used to help mitigate this. Due to ease of collection, peripheral blood (PB) stem cells are increasingly being considered for haplo-HCT. We retrospectively analyzed 74 patients (42 BM and 32 PB) who underwent haplo-HCT at Ohio State University from 2009 to 2018. Median age at transplant was 60 years (yrs) for BM and 54 yrs for PB, (p = 0.45). There was no difference in OS (p = 0.13) and NRM (p = 0.75) as well as PFS (p = 0.10) or GRFS (p = 0.90) between the groups. The BM cohort showed a 3-year OS rate of 63% (95% confidence interval (CI): 46–76), and 3-year PFS of 49% (95% CI: 33–63). For the PB group, 3-year OS and PFS were 78% (95% CI: 59–89) and 68% (95% CI: 49–82), respectively. There were no differences in the incidence of acute GVHD (grade II-IV) (p = 0.31) and chronic GVHD (p = 0.18). Patients receiving BM had a significantly higher risk for relapse with relapse rates by 2 years at 36% (95% CI: 22–50) vs. 16% (95% CI: 6–31) for PB (p = 0.03). The findings from this study suggest that PB is an excellent alternative to BM for haplo-HCT.