“Longterm Survival (≥10 years) in Multiple Myeloma (MM) Is Associated with Longer Duration of Therapy and Improved Quality of Response to Novel agents”.

Over the past decade, survival of MM patients (pts) has improved significantly, with median survival currently estimated at 4-4.5 years (yrs). Much of this improvement can be attributed to the introduction of novel agents such as bortezomib and the immunomodulatory drugs in the late 1990's (Kumar et al, Blood 2008). Despite these therapeutic advances, long-term survivors of ≥10 yrs in MM are uncommon and account for <10% of pts. In this report, we identified 39 MM pts diagnosed over a 4 yr period (1994-1998) at our institution who have survived ≥10 yrs and aimed to define disease/treatment characteristics.

Between January 1994 and November 1998, 39 MM pts diagnosed at Princess Margaret Hospital were identified as long-term survivors (≥10 years) with median follow-up of 12.3 years (range 11.2-13.6 yrs). Pt demographics, disease and treatment characteristics, and response outcomes were collected from a MM database and by retrospective chart review. An additional 47 MM pts diagnosed during the same 4 year time frame with <10 year survival were reviewed as controls. The median follow-up for these control pts was 6.9 yrs (range 5.3-8.3).

Patient and disease characteristics: Median age at diagnosis for the 39 long-term survivors was 51 yrs (range 46-57), 22 pts (56%) male. Myeloma subtypes included: IgG 21(54%), IgA 9(23%), IgD 1(3%), light chain only 6(15%), Non-secretory 2(5%). Most pts (97%) had undergone autologous stem cell transplantation (ASCT), 13 of whom (37%) received a second salvage transplant at relapse. Median age at first transplant was 53 yrs (range 45-61). At diagnosis, 27 pts (73%) had bone lesions and only 1 pt (2.6%) had renal failure (serum creatinine ≥177umol/L (2mg/dL). Baseline lab values at diagnosis: median hemoglobin 115g/L (range 45-149), WBC 5.2/uL (range 3.1-9.4), platelets 230/uL (range 153-402), creatinine 90umol/L(52-315), beta2-microglobulin 145 nmol/L (range 43-391; normal <170), BM plasmacytosis 51% (range 15-80). Cytogenetics were not routinely available. No differences in baseline variables were noted from the 47 control pts diagnosed during the same 4 year period.

Treatment characteristics: Of all 86 pts, 54 pts (63%) were exposed to one or more of the novel agents including thalidomide (59%), bortezomib (31%) and lenalidomide (39%). During the time period when first relapse was anticipated, thalidomide was the primary novel agent available at our institution. Although significantly fewer longterm survivors vs controls received thalidomide (41 vs 79%; p=0.002), the duration of thalidomide exposure was significantly longer with the long-term survivors (median 28 vs 8.5 mos; p=0.03). The lower rates of thalidomide exposure in longterm survivors were not explained by earlier introduction of either lenalidomide or bortezomib to this group with longer time to both bortezomib and lenalidomide in the long-term survivors. In fact, time from diagnosis to exposure to any of the 3 novel agents was significantly longer for the long-term survivors than the control group (88mos (range 35-169) vs 67mos (range 13-133); p=0.009). However, as with thalidomide, long-term survivors were exposed to bortezomib for longer duration than the control group (median 5 vs 2 mos; p=0.009). No difference in rates or duration of exposure to lenalidomide between the 2 groups was noted. Of note, long-term survivors were more likely to have responded to any of the 3 novel agents (overall response 83% vs 53%, p=0.02) and were able to achieve a better quality of response than the control group (VGPR/CR 38% vs 3%; p=0.003).

Long-term survivors of MM (≥10 years) are uncommon, even in the current era of novel agents (thalidomide, bortezomib, lenalidomide). In our review, we did not find that exposure alone or earlier use of novel agents (ie. shorter time from diagnosis to any novel agent) was associated with long-term survival. However, when compared to MM pts living <10 yrs, long-term survivors had significantly longer duration of exposure to novel agents and were able to achieve higher rates of response with better quality of responses (VGPR/CR). Our data support the hypothesis that prolonged therapy may be required to achieve durable and high quality responses in MM pts. Hence, further studies of “maintenance” schedules are warranted.

No relevant conflicts of interest to declare.