Geriatric assessments and frailty scores in multiple myeloma patients: a needed tool for individualized treatment?

PURPOSE OF REVIEW: Multiple myeloma is a disease of elderly adults. Improvement in survival has occurred because of biological insights and novel agents. Therapeutic options involve choices today, thus have become more complex. Demographics have led to an increased number of elderly patients and age may be associated with a poorer outcome but is not the only prognostic predictor today. RECENT FINDINGS: To evaluate patients' health status rather than their chronological age alone, frailty scores and functional geriatric assessments are used to identify prognostic groups, avoid adverse events, compare clinical trials and tailor treatment. As most clinical trials exclude frail elderly patients, those enrolled therein are often younger and healthier than the typical multiple myeloma patient. This represents a challenge for frail cohorts because of their increased risk of adverse events, overtreatment and undertreatment and/or therapy discontinuation, which may lead to poorer survival and quality of life (QoL). Reassessing patients' status via geriatric assessments is also relevant during treatment to adjust interventions appropriately. SUMMARY: Integrating geriatric assessments may lead to individual treatment decisions, dose adjustments, better clinical outcome and QoL. Prospective clinical trials that enroll elderly multiple myeloma patients with comorbidities, incorporate frailty scores/geriatric assessments and help with prognostication, adverse event avoidance and QoL maintenance, remain warranted.

Multidisciplinary tumor boards and their analyses: the yin and yang of outcome measures.

BACKGROUND: The standard to ensure utmost cancer treatment is a prerequisite in national cancer plans for comprehensive cancer centers (CCCs) and ensured through multidisciplinary tumor boards (MTBs). Despite these being compulsory for CCCs, various analyses on MTBs have been performed, since MTBs are resource-intensive. Outcome measures in these prior analyses had been survival (OS), MTB-adherence and -satisfaction, inclusion of patients into clinical trials and better cancer care. MAIN BODY: A publication from Freytag et al. performed an analysis in multiple tumor entities and assessed the effect of number of MTBs. By matched-pair analysis, they compared response and OS of patients, whose cases were discussed in MTBs vs. those that were not. The analysis included 454 patients and 66 different tumor types. Only patients with > 3 MTBs showed a significantly better OS than patients with no MTB meeting. Response to treatment, relapse free survival and time to progression were not found to be better, nor was there any difference for a specific tumor entity with vs. without MTB discussions. An in-depth discussion of these results, with respect to the literature (PubMed search: "MTBs AND cancer") and within the author group, including statisticians specialized in data analysis of cancer patients and questions addressed in MTBs, was performed to interpret these findings. We conclude that the results by Freytag et al. are deceiving due to an "immortal time bias" that requires more careful data interpretation. CONCLUSIONS: The result of Freytag et al. of a seemingly positive impact of higher number of MTBs needs to be interpreted cautiously: their presumed better OS in patients with > 3 MTB discussions is misleading, due to an immortal time bias. Here patients need to survive long enough to be discussed more often. Therefore, these results should not lead to the conclusion that more MTBs will "automatically" increase cancer patients' OS, rather than that the insightful discussion, at best in MTBs and with statisticians, will generate meaningful advice, that is important for cancer patients.

Pomalidomide combinations are a safe and effective option after daratumumab failure.

PURPOSE: Outcomes of multiple myeloma (MM) patients who are refractory to daratumumab are dismal and no standard of treatment exists for this patients' population. Here, we investigate the role of pomalidomide combinations in daratumumab-refractory MM patients. METHODS: We performed a retrospective analysis of myeloma patients treated at four referral centers (three in Germany and one in Italy). Review chart identified 30 patients with relapsed and refractory myeloma, who progressed during treatment with daratumumab and were treated with pomalidomide-based combinations in the subsequent lines of therapy. RESULTS: Responses improved from 37% with daratumumab to 53% with pomalidomide. Of seven patients with extramedullary MM (EMM), four achieved a clinical stabilization with pomalidomide, including one patient with a long-lasting complete response. Median progression-free survival and overall survival were 6 and 12 months, respectively. Pomalidomide combinations were well tolerated, no patient discontinued treatment due to adverse events. CONCLUSION: These data show that pomalidomide-based combinations can be an effective and safe salvage regimen for daratumumab-refractory patients, including those with EMM.

Choosing the Right Therapy for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Consideration of Patient-, Disease- and Treatment-Related Factors.

Treatment of relapsed/refractory multiple myeloma (RRMM) is more complex today due to the availability of novel therapeutic options, mostly applied as combination regimens. immunotherapy options have especially increased substantially, likewise the understanding that patient-, disease- and treatment-related factors should be considered at all stages of the disease. RRMM is based on definitions of the international myeloma working group (IMWG) and includes biochemical progression, such as paraprotein increase, or symptomatic relapse with CRAB criteria (hypercalcemia, renal impairment, anemia, bone lesions). When choosing RRMM-treatment, the biochemical markers for progression and severity of the disease, dynamic of disease relapse, type and number of prior therapy lines, including toxicity and underlying health status, need to be considered, and shared decision making should be pursued. Objectively characterizing health status via geriatric assessment (GA) at each multiple myeloma (MM) treatment decision point has been shown to be a better estimate than via age and comorbidities alone. The well-established national comprehensive cancer network, IMWG, European myeloma network and other national treatment algorithms consider these issues. Ideally, GA-based clinical trials should be supported in the future to choose wisely and efficaciously from available intervention and treatment options in often-older MM adults in order to further improve morbidity and mortality.