Kelly N. Godby

Recent trends in multiple myeloma incidence and survival by age, race, and ethnicity in the United States

Prior improvements in multiple myeloma (MM) survival were not fully observed in racial and ethnic minorities and older individuals. We hypothesized that improvements in MM management in recent years have reduced these disparities. We used the Surveillance, Epidemiology, and End Results registries to calculate the incidence and relative survival rates (RSRs) of MM in the United States for patients diagnosed from 1993 to 1997 (prethalidomide), 1998 to 2002 (introduction of thalidomide), 2003 to 2007 (bortezomib and lenalidomide), and 2008 to 2012 (upfront bortezomib and lenalidomide, early availability of carfilzomib and pomalidomide). MM incidence increased significantly among non-Hispanic whites (NHWs) and non-Hispanic black (NHB) men, but not among NHB women and Hispanics. Improvement in 5-year RSRs (1993-1997 vs 2008-2012) was seen among patients of all age and race/ethnicity groups. Ten-year RSRs (1993-1997 vs 2003-2007) improved for patients <65 years of age (19.6%-35%; P < .001), but not for patients ≥75 years of age (7.8%-9.3%; P = .3). Among patients 65 to 74 years of age, 10-year RSRs improved for NHWs (11.3% vs 20.5%; P < .001) and Hispanics (10.6% vs 20.2%; P = .02), but not for NHBs (12.6% vs 19.5%; P = .06.). These findings confirm consistent improvement in survival for MM patients and point to the challenge of further extending these improvements to older and minority patients.

Abstract 1299: Effect of family history of cancer on the risk of multiple myeloma: Differences by ancestry and age of onset

Background. Multiple myeloma (MM) is the most common hematologic malignancy affecting African Americans, with a younger age of onset and standardized incidence and mortality rates that are twofold higher compared to European Americans despite the presence of clinical features, which are consistent with milder clinical course. The basis for this paradox remains poorly understood. However, evidence suggests a shared genetic susceptibility. Methods. Using 720 participants (259 confirmed MM cases; 461 age-, sex-, ancestry-matched controls) enrolled in the Molecular and Genetic Epidemiology (iMAGE) study of myeloma, we examined the risk of MM associated with a positive family history of cancer and the excess risk observed among AA patients. Family history of cancer was obtained from structured interviews and risk estimates were calculated using odds ratios (OR) and corresponding 95% confidence intervals (CI) from logistic regression stratified by ancestry and median age of MM onset (65 years). Results. Of the total participants included (42% African American), the majority reported a positive family history of cancer (80%), including solid tumors (75%), hematologic malignancies (17%) and MM (4%). A positive family history of any cancer in any relative was strongly associated with an increased risk of MM overall (OR=1.73, 95% CI 1.14-2.60; P=0.008), as well as among African Americans (P=0.03) and participants less than 65 years of age (P=0.0005). MM risk was markedly increased for participants who reported any relative with MM overall (OR=3.06, 95% CI 1.42-6.58; P=0.004) and among participants less than 65 years of age (OR=4.06, 95% CI 1.44-11.5; P=0.005). The magnitude of this effect was greater in African Americans (OR=18.6, 95% CI 2.32-148; P=0.0002) compared to European Americans, and was notable among first-degree relatives (OR=9.90, 95% CI 1.14-85.9; P=0.01). In contrast, MM risk was not significantly elevated for participants who reported relatives with any hematologic malignancy other than MM (OR=1.47, 95% CI 0.96-2.27; p=0.08) nor a positive family history of solid tumors (OR=1.36, 95% CI 0.95-1.95; P=0.09), and these estimates did not differ by ancestry, age of onset or degree of relative. Conclusions. Our observations suggest that the excess risk of MM observed among African Americans and among those with early age of onset may be attributed to shared susceptibility including underlying heritable genetic and environmental factors. Future studies are warranted to examine the relationship between family history of MM with clinical and cytogenetic factors, which are known to differ by ancestry. Citation Format: Gwendolyn I. Pruitt, Howard W. Weiner, Racquel D. Innis-Shelton, Donna Salzman, Kelly N. Godby, Vishnu B. Reddy, Fady M. Mikhail, Andrew J. Carroll, Elizabeth E. Brown. Effect of family history of cancer on the risk of multiple myeloma: Differences by ancestry and age of onset. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1299. doi:10.1158/1538-7445.AM2014-1299

Second primary malignancy after multiple myeloma-population trends and cause-specific mortality

The management of multiple myeloma (MM) has evolved with the increased use of autologous haematopoietic cell transplantation (AHCT) and the introduction of new agents. AHCT and lenalidomide maintenance have been associated with increased risk of second primary malignancy (SPM). We iseutilised the Surveillance, Epidemiology and End Results 13 registries to analyse 9 833 patients diagnosed at age <65 years for three eras: 1995–99 (pre‐thalidomide, limited use of AHCT), 2000–04 (post‐thalidomide, pre‐lenalidomide and bortezomib, increased isautilisation of AHCT) and 2005–09 (post‐lenalidomide and bortezomib, higher isautilisation of AHCT). Changes in risk of SPM were assessed by utilising standardised incidence ratio (SIR) and cause‐specific risk of death. Cumulative incidence of SPM at 90 months was 4·7%, 6·0% and 6·3% respectively, P = 0·0008. SIR for haematological malignancies in years 1–5 increased, from 1·28 (95% confidence interval [CI] 0·47–2·78) in 1995–99 to 2·17 (95% CI: 1·27–3·48) in 2005–09, due to increased risk of acute leukaemias and lymphomas. A similar trend was observed in years 6–10. Overall mortality in patients with MM declined sharply over time due to declines in MM‐associated and cardiovascular mortality with no increase in risk of death from SPM. The evolution of MM therapy is linked to population‐level increase in risk with no discernible effect in death from SPM.

Phase 1/2 Trial of Carfilzomib Plus High-Dose Melphalan Preparative Regimen for Salvage Autologous Hematopoietic Cell Transplantation Followed by Maintenance Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma

We performed a phase 1/2 trial to investigate the safety and activity of the second-generation proteasome inhibitor Carfilzomib (K) on days -3/-2 in combination with melphalan 200 mg/m2 (MEL200) on day -2 (K-MEL) in patients with relapsed multiple myeloma (MM) undergoing autologous hematopoietic cell transplantation (phases 1 and 2). Patients without progression received 12 cycles of K maintenance at 36 mg/m2 days 1, 8, and 15 (schedule A) or days 1, 2, 15, and 16 (schedule B), with patients being treated for 2 cycles in each schedule and on the patient-preferred schedule for the remaining cycles (phase 2). The patients had received a median of 3 previous lines of therapy, 56% had undergone previous AHCT, and 51% had received previous K therapy. During phase 1 (n = 15), the maximum tolerated dose of K in combination with MEL200 was not reached, so the maximum tested dose of 27 mg/m2 (on day -3) and 56 mg/m2 (on day -2) was used in phase 2. The rate of very good partial response after K-MEL therapy (n = 44) was 59.2%, compared with 13.7% before K-MEL therapy. Among patients starting maintenance therapy (n = 27), 12-month progression-free survival was 66.7% and 12-month overall survival was 88.1%. There was no strong patient preference for either schedule. Two patients discontinued maintenance due to toxicity. K-MEL followed by K maintenance is safe and active salvage therapy in patients with MM.