How I treat elderly patients with plasma cell dyscrasias

Abstract

Plasma cell dyscrasias are a rare heterogeneous group of hematological disorders which are more prevalent in the older part of the population. The introduction of novel agents, improved understanding of disease biology and better supportive management have improved outcomes considerably and in the era of the aging population the question of how to best manage older patients with plasma cell dyscrasias has never been more relevant. Data on how to treat these patients comes mostly from subgroup analysis as they are underrepresented in clinical trials. This review will cover issues, available evidence and recommendations relevant to diagnosis and management of the older patients with Multiple Myeloma (MM), Waldenstrom Macroglobulinemia (WM) and systemic AL Amyloidosis. What will become increasingly evident is the need to develop and establish the use of disease-specific geriatric assessment (GA) tools. Frailty status assessment using GA tools and moving away from making decisions based merely on chronological age will allow setting clear treatment goals and consequently achieving an optimum balance between effectiveness and toxicity for this complex and heterogeneous group of patients.

Keywords: AL amyloidosis; Multiple Myeloma; Waldenstrom Macroglobulinemia; elderly patients; frailty.

Figure 1

Recommendations for the treatment of newly diagnosed patients with Waldenstrom’s Macroglobulinemia. Figure adjusted from ESMO guidelines for WM 2018 and EMN recommendations for treatment of rare plasma cell dyscrasias. *Approved in USA by FDA for first line and only for patients unfit for immunochemotherapy in Europe by EMA. ** BR for unfit patients may require dose reductions for bendamustine and use of G-CSF and antibiotic prophylaxis. BDR: bortezomib, dexamethasone, rituximab, BR: bendamustine, rituximab; DRC: dexamethasone, rituximab, cyclophosphamide; AF: atrial fibrillation, V: bortezomib.

Figure 2

Recommendations for the treatment of previously treated patients with Waldenstrom’s Macroglobulinemia. Figure adjusted from ESMO guidelines for WM 2018 and EMN recommendations for treatment of rare plasma cell dyscrasias. R: rituximab.

Figure 3

Risk adapted treatment recommendations in systemic AL amyloidosis. Adapted from Palladini et al 2016(115) and Gavriatopoulou et al 2018. Data mainly comes from uncontrolled trials. ASCT: autologous stem cell transplant, DLCO: lung diffusion of CO, EF: ejection fraction, MEL: melphalan, NYHA: New York Heart Association, OS: performance status by ECOG, sBP: systolic blood pressure, Stage is Mayo Clinic cardiac stage, VCD: velcade+cyclophosphamide+dexamethasone, CD: velcade+ dexamethasone, MDex: melphalan+dexamethasone, CR: complete response, PI: proteasome inhibitor, BMDex: bortezomib+ melphalan+dexamethasone.