Presentation Characteristics, Risk Profiles and Response to Thalidomide in a Public Health System, Minority Patient Population with Multiple Myeloma
Authors: Sreenivasappa Shylendra B , Shah Mousami , Catchatourian Rosalind , Fochesatto Luciano , Yim Barbara 
Published: April 2020

Background: Multiple Myeloma is a clonal plasma cell malignancy which accounts for about 10% of all hematological malignancies. Introduction of thalidomide has revolutionized the treatment. We have characterized the risk profiles and response to thalidomide in a minority cohort socio-economically ineligible for stem cell transplant.

Methods: 113 patients (pts) with Multiple myeloma who were treated with thalidomide between the periods of 2002–2008 were identified and studied as a retrospective cohort. Demographics, presentation, dosage schedule, tolerability and response were analyzed. Categorical data via Fisher’s exact test and time to progression data was analyzed via Kaplan Meier life table analysis and log rank test.

Results: Demographic and disease characteristics of 113 pts are as follows: 73 (64.6%) females, 40(35.4%) males, 71(62.8%) african american, 23(20.4%) hispanic, 10(8.8%) caucasian and 9(8%) others. The median age at diagnosis was 58.5 years, with 86(76.1%) being 65 or younger and 27 (23.9%) older than 65. 90(79.6%) pts had 2 or less co morbidities. 99(87.6%) pts could not receive stem cell transplant. Bone pain was the most common presenting symptom (35%). 68 had lytic lesions (60%). 21(18.6%) pts were Durie Salmon stage I, 26(23%) stage II, 56(49.5%) Stage III and 10 had missing data. 65(57.5%) had IgG disease, 27(23.8%) IgA and 20(17.7% light chain disease. 64 (56.6%) pts had received a prior therapy. Almost all patients received thalidomide and dexamethsone. Thalidomide was started at 50 or 100mg and the dose was escalated by 50 mg upon progression. 54 (47.8%) pts were started on 50 mg of thalidomide, 55 (48.7%) on 100mg, 3 (2.7%) on 200mg and 1 (0.9%) on 150mg. Thalidomide was discontinued either due to intolerance or disease progression. Patients receiving 50 mg of thalidomide as starting dose (n=54), had an overall response rate (ORR) of 61%. Of these 4 (7.4%) had VGPR, 10 (18.5%) PR and 19(35.2%) stable disease (SD). Median time to dose escalation was 4 months (range 1–36 months). 19 pts were dose escalated to 100mg and achieved an ORR of 79%. Of these 19 pts, 11(57.8%) had SD, 4 (21%) had PR and 4 (21%) had progression of disease. The mean duration of thalidomide therapy in this sub group was 9.94 months. 10 deaths were noted in the group.

In pts on 100mg of thalidomide upfront, (n=55) ORR was 69.1%.1 pt (1.8%) had a CR, 3 (5.5%) had VGPR, 18 (32.7%) had PR and 16 (29.1%) had SD. The median time to dose escalation was 7 months (range 1–84 months). Thalidomide dose was increased in 8 pts and ORR of this subgroup was 50%, 1 pt (12.5%) had a CR and 3 (37.5%) had SD. The median duration of therapy in this sub group is 19.5 months and 8 deaths were noted.

In the entire cohort the overall response rate to thalidomide and dexamethasone was 69.1%. The median duration of therapy was 8 months (range of 1 to 84 months) and median follow up was 22 months (range 1 to 173). The incidence of grade 3 and grade 4 toxicity are as follows: 12 (10.5%) had neurologic, 2(1.8%) had constitutional side effects, 3 (2.5%) gastrointestinal, 5 (4.4%) venous thromboembolism. 7 (6.3%) infection related complications, 3(2.7%) musculoskeletal, 3 (2.7%) had renal. We documented 18 deaths (12 stage III and 6 stage II). Aspirin for DVT prophylaxis was used in 80(70.8%) pts, coumadin in 4 (3.5%).

Discussion: In our minority cohort the median age at diagnosis was much younger than the historical control (58.5 yr vs 62). More than 75% of pts were younger than 65 years and more than half presented with advanced stage. The frequency of monoclonal immunoglobulin was similar to historical controls and so was the overall response to treatment. The incidence of adverse events was much lower than historical controls and this was inspite of longer duration of thalidomide therapy.

Conclusion: Ethnic minority patients present with advanced disease and at younger age. Transplant ineligible patients may benefit from a stepwise increment in the dosing of thalidomide and this may account for fewer side effects even on prolonged therapy. Step wise dosing schedule needs to be tested in a prospective randomized trial.