The Outcomes of Elderly Multiple Myeloma Patients Treated in the United States

Background

Improvements in the prognosis for elderly multiple myeloma (MM) patients have been less pronounced than those of younger, autologous transplant-eligible patients. The latter do not typically receive low-dose, oral melphalan-based regimens, which are less potent, slower in onset of activity, and possibly more myelosuppressive than novel agents. Indeed, the FIRST phase 3 study comparing lenalidomide and dexamethasone (RD) to melphalan, prednisone, and thalidomide (MPT) has already demonstrated a significant improvement in progression free survival (PFS) with a trend towards improved overall survival (OS), though longer follow up will be required.

To date, there are very limited data for the outcomes of elderly MM patients with doublet regimens let alone triplet regimens in the United States, where drug availability is significantly different from other parts of the world. In this single-institution, retrospective study, we obtained data from a substantial cohort of elderly U.S. patients, most of whom received novel agent-based initial therapy, though with significant planned dose attenuations.

Methods

The inclusion criteria for this study were patients over the age of 70 at the time of diagnosis of symptomatic MM with at least one year of follow up. The patients were seen at St. Vincent's Catholic Medical Center and subsequently Mount Sinai Hospital between 1998 and 2013. Of the 133 consecutive charts reviewed, 16 were eliminated due to incomplete records.

Results

Of the 117 patients who met the eligibility criteria, the median age was 75 years (range 70 – 95). There were significant baseline comorbidities including 36% cardiac, 20% renal (CrCl < 30 mL/min), and 5% pulmonary disease. Of the 79 patients with ISS information, 36% were stage III, and of the 68 patients with cytogenetics/FISH information, 9% were high-risk. The median follow up was 43 months (1 – 154 months), and the median number of lines of therapy was 2 (1-7).

Excluding 4 patients who received corticosteroids alone, 95 patients out of 113 (84%) received non-melphalan doublet, triplet, or quadruplet initial therapy (see Table 1). For those treated with RD plus bortezomib (RVD), despite significant dose attenuations (78% received 1.3 mg/m²V SQ once weekly and 76% received < 15 mg R), the outcomes were particularly impressive with ORR, CR+VGPR, and PFS of 94%, 65%, and 36 months, respectively, and OS not reached. Despite the percentage of ISS Stage III and high-risk cytogenetics/FISH being balanced across the groups, PFS with RVD was significantly greater than that of all other regimens (p=0.030). When comparing RVD and RD patients, the PFS was superior for the RVD group (p=0.047).

Conclusions

This study is the largest to date that examines outcomes of elderly MM patients from the United States where the majority of subjects received non-melphalan-containing initial regimens. Similar to the FIRST study, our novel agent outcomes compare favorably to the average RR, CR, PFS, and OS of the 5 large studies on MP and MPT (39%, 2.6%, 15 and 30 months and 66%, 11%, 20.7 and 39.2 months, respectively). Dose-attenuated RVD was associated with the best outcomes of any induction therapy.

Although the inherent limitations of a retrospective study preclude definitive causal attribution, particularly given a possible referral bias for patients seen at an academic referral center, the inclusion of all consecutive patients (including many with comorbidities that would not meet standard clinical trial eligibility criteria) provides important real world data. In particular, the median OS for all elderly U.S. MM patients in this study was 113 months (95% CI of 70.0 – 156.3 months). This is likely due to a combination of improved outcomes attained by using induction therapies used in younger patients as well as readily available salvage regimens.

^{*CR unconfirmed}

^{**Includes 4 patients whose regimens were corticosteroid-only}