Explore Data

Management of newly diagnosed multiple myeloma (NDMM)

Over the past 20 years the MM treatment landscape has greatly expanded. Advances include new modalities that target different aspects of MM pathophysiology, leading to deeper responses and positive outcomes for patients.1–3

To review the most up to date MM treatment regimens, visit the Guidelines page.

Therapies for MM2

HDAC Inhibitors
img

The first step in treating newly diagnosed (ND) patients is determining whether they are a candidate for autologous stem cell transplant (ASCT). Typically, ASCT is Standard of Care (SoC) for patients up to 65 years of age, but performance status (PS), comorbidities and patient preference must also factor into this decision. Induction regimens are used to induce a deep response prior to the patient receiving high dose chemotherapy followed by the reinfusion of stem cells. Triplet induction regimens have shown improved responses over traditional doublet combinations but may also be associated with greater toxicities. The choice of induction regimen requires a careful balance between efficacy and adverse events. The use of lenalidomide maintenance therapy following ASCT has become SoC. The study of additional agents in the ASCT setting continues, including proteasome inhibitors, immunomodulators, and anti-CD38 and SLAMF7 monoclonal antibodies.1

For those who cannot tolerate transplant, treatment is intended to control symptoms, preserve vital organ function, maintain PS and maximize QoL. Treatment regimens are highly individualized and can include combination therapies at various dosing levels based on the patient’s fitness. Careful clinical assessment is required, as an ASCT-ineligible patient may still be able to undergo a triplet regimen at full dosage to maximize treatment benefits. Navigating the number of options in this space makes decisions around treatment especially complex.

There are still many unanswered questions in the field of NDMM. Modulating the bone marrow microenvironment to reverse immune tolerance of MM cells has proved challenging, with early trials of established immunotherapies such as PD-1 and PD-L1 inhibitors having failed to produce positive results in early phase clinical trials.2 Other fields of investigation include the influence of the gut microbiome on the response of MM to treatment and identification of response biomarkers.2

Conclusion

The expansion of therapeutic options has transformed outcomes for MM patients. However, each new agent approved within the treatment space brings additional questions and complexity. RWE provides us with another piece of the puzzle and further improves our understanding of how best to implement these new therapies in the care of MM patients by providing additional insights into the outcomes that can be achieved when these treatments are prescribed for patients being treated in routine clinical practice.3

References

1. Goldschmidt H et al. Ann Hematol. 2019;98(1):1-18. 2. Gulla A et al. Haematologica. 2020;105(10):2358-2367. 3. Cavo M et al. Expert Rev Hematol. 2018;11(3):219-237.

Abbreviations

ACT, adoptive T-cell; ASCT, autologous stem cell transplantation; BiTE, bispecific T-cell engager; BMEC, bone marrow endothelial cell; BMM, bone marrow microenvironment; BMSC, bone marrow stromal cell; CAR-T, chimeric antigen receptor; CD38, cluster of differentiation 38; CELMoD, cereblon E3 ligase modulator; DC, dendritic cell; ECM, extracellular matrix; HDAC, histone deacetylase; IMiD, immunomodulatory drug; IRF4, interferon regulatory factor 4; MM, multiple myeloma; ND, newly diagnosed; NDMM, newly diagnosed multiple myeloma; NK, natural killer; OB, osteoblast; OC, osteoclasts; PD-1, programmed cell death 1; PD-L1, programmed cell death ligand 1; pDC, plasmacytoid DC; PS, performance status; QoL, quality of life; RWD, real‑world data; SLAMF7, signalling lymphocytic activation molecule family 7; SoC, standard of care; Treg, regulatory T-cell; TCR, T-cell receptor; MDSC, myeloid-derived suppressor cell;