Tolerance and Response to Initial Systemic Therapy In Older Patients with Multiple Myeloma (MM): Observations From 276 Unselected Recent Cases In the Practices of US-Based Medical Oncologists (MOs)

MM is generally considered incurable, but the rapid integration of IMiDs^.. and proteasome inhibitors into systemic anticancer treatment (SAT) has resulted in clinically important improvements in response rates, disease control and overall survival. A number of factors — including age and comorbidities — influence selection of an initial SAT and whether autologous stem cell transplant (ASCT) is planned. A paucity of information exists on selection of specific SATs for patients in different age groups and resultant outcomes. We attempted to address this issue by aggregating and examining clinical information on individual patients receiving initial treatment for MM.

US community-based MOs were recruited from a database of past participants in our CME activities to provide anonymous information on the presenting symptoms, diagnostic workup, treatment selection, side effects and clinical antitumor response for all patients in their practices with a new diagnosis of MM since January 1, 2008. Modest, per-patient honoraria were provided to each MO for this work.

From April 14 to July 9, 2010, 43 MOs entered a total of 276 cases of MM into a web-based data bank (minimum 1 case, maximum 14, median 6). 54% of the patients were men. The median age was 68, with 34% under age 65, 36% from 65 to 74 and 30% age 75 or older.

88% of patients had their tumors evaluated by FISH and/or metaphase cytogenetics. 73% of the evaluated specimens were considered to be “standard risk” and 27% were determined to be “poor risk.” 67% of patients were considered very or moderately symptomatic from the disease at the time treatment was initiated (Table 1), and similar fractions of patients presented with various levels of symptomology across the three age groups.

128 patients (46%) were deemed eligible for ASCT (maximum age 78), and 59 of these patients had already received ASCT after induction treatment. The median age of patients eligible for ASCT was 62, and the most common induction SATs for these patients were Rd or RD (29%), RVD (26%) and VD (23%). The median age of patients considered ineligible for transplant was 76.5, and the most common induction SATs were VD (22%) Rd or RD (21%) MPT (17%) and MPV (17%).

Overall, these treatments resulted in CR and PR rates of 22% and 64% respectively, and “things went very well with expected or fewer toxicities” in 38% and minor or moderate toxicity in 44%. These outcomes are similar to what has been reported in published trial data from randomized Phase III studies of these regimens. No major differences were observed in reported levels of efficacy and side effects among the three age groups (Table 1).

This unselected case series produced, in a rapid manner, useful information addressing a variety of clinical issues in newly diagnosed MM, including the impact of age and transplant status on treatment selection and outcomes. These data suggest that MOs are able to individualize SATs for older patients and match the short-term outcomes of the therapies they select for younger patients. This risk-benefit differential is of particular palliative importance as these data demonstrate that at diagnosis most patients present with tumor-related symptoms. Additional work of this kind is needed to better understand how physicians adjust doses and schedules of SATs to prevent and ameliorate toxicity, particularly in older patients.

Lonial:Bristo-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium Pharmaceuticals Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Anderson:Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millenium Pharmaceuticals Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onxy Pharmaceuticals Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees. Fonseca:Amgen Inc: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene Corporation: Consultancy, Research Funding; Genzyme Corporation: Consultancy; Medtronic Inc: Consultancy; Otsuka Pharmaceutical Co Ltd: Consultancy; Onyx Pharmaceuticals: Research Funding.