Maximal response to infusional chemotherapy prior to autotransplantation influences outcome of patients with newly-diagnosed multiple myeloma

R. Powles*, B. Sirohi, J. Treleaven, S. Singhal, S. Kulkarni, I. Chau, R. Saso, C. Horton, R. Lal, J. Mehta

*Corresponding author for this work

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1 Scopus citations

Abstract

From a prospectively maintained database, we identified 280 newly-diagnosed patients with myeloma (30-84 y median 53; 174 M, 106 F) between 4/85 and 8/99 who received sequential therapy comprising infusional chemotherapy (1C) with VAMP (n=69)/CVAMP(n=175)/V-CVAMP(n=36) (vincristine, doxorubicin, methylprednisolone with or without cyclophosphamide/verapamil) followed by consolidation with high-dose therapy (HOT) and interferon-a2b maintenance. 175 patients had IgG, 43 IgA and 62 light-chain disease. 205(73%) patients had stage II1A/B; median creatinine 93 nmol/L (range, 45-1463); median 2M 3.8 mg/L (range, 0.6-48.6); bone lesions >2:190 (68%). Courses of 1C were repeated 3 weekly till maximum response and were then followed by an additional course. Response was assessed after 2,4 and 6 courses. The median number of courses was 5(range, 1-12). Post-IC, 38 (14%) patients achieved complete remission (CR), 155 (55%) partial remission (PR), 63 (22%) non-responders (NR) and 24 (9%) died. Cox analysis of variables at presentation for the probability of attaining CR after 1C chose only 2M<3.8 mg/L (RR0.5, P=0.04) as an independent factor. Cox regression model chose less than 5 courses of 1C (RR-0.3; P=0.001) as the only independent variable highly predictive of attaining CR when this was introduced as one of the variables alongwith the presentation ones. 209/280 (75%) received HOT evenly distributed between CR, PR and NR patients (P=0.3). Median overall survival for CR patients post-IC was 7.9y (95%Cl:26-65), 4.4y (95%CI:41-58) for PR and 2.7y (95%CI:35-60) for NR (P=0.001) and the median event-free survival for CR patients post-IC was 3.3y (95%CI:31-65), 2.3y (95%CI:41-57) for PR and 1.3y (95%CI:36-61) for NR (P<0.0001 ). Patients achieving CR post-IC (n=38) when compared to those who achieved CR after HOT (n=72) had a longer EPS (3.3y vs 2.8y; P=0.05) though the OS was comparable from the time of 1C. 21/38(55%) patients who achieved CR after 1C relapsed; 12 were retreated with 1C and none of these attained CR with 1C- 7 NR and 5 PR. It remains an enigma why patients so responsive to 1C the first time around become relatively so resistant to reinduction. We conclude that patients who attain CR on IC and proceed to high-dose therapy have better outcome and those patients who require more than 5 courses of IC potentially had more resistant disease, a fact quite similar to acute lymphoblastic leukemia whore patients in CR within 14 days of starting treatment fare better than slow responders.

Original languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART II
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Hematology

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    Powles, R., Sirohi, B., Treleaven, J., Singhal, S., Kulkarni, S., Chau, I., Saso, R., Horton, C., Lal, R., & Mehta, J. (2000). Maximal response to infusional chemotherapy prior to autotransplantation influences outcome of patients with newly-diagnosed multiple myeloma. Blood, 96(11 PART II).