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1.
Blood Adv ; 2(22): 3102-3111, 2018 11 27.
Article in English | MEDLINE | ID: mdl-30455359

ABSTRACT

Few reports assess prognosis during follow-up of patients with symptomatic Waldenström macroglobulinemia (WM). In 121 WM patients treated between 1993 and 2016, we analyzed the prognostic role during the clinical course of the initial International Prognostic Scoring System for WM (IPSSWM). Then, we assessed onset of response, progression, and second treatment initiation coded as time-dependent covariates. High-risk IPSSWM was an adverse prognostic factor for survival after first treatment initiation (SAFTI). Nevertheless, the corresponding Dxy concordance index obtained in multiple landmark analyses decreased from 0.24 to 0.08 during the first 6 years, in accordance with a departure from the proportional hazard assumption. By contrast with onset of response (whatever its level), onset of progression and initiation of second-line treatment retained prognostic value for SAFTI (P = .02 and P = .006, respectively). These findings were confirmed in cause-specific Cox models for deaths related to WM, but not for unrelated deaths. Time to progression after first-line treatment and time to initiation of second-line treatment had no prognostic value for survival after these 2 events. These results were confirmed in an independent series of 119 patients homogeneously treated with chemoimmunotherapy. Finally, after second-line and third-line treatment, onset of progression had significant prognostic value for subsequent risk of related death only. Thus, taking initial IPSSWM and delayed response to treatment into account, only onset of progression and second treatment initiation provided additional prognostic information for SAFTI. Therefore, progression-free survival or time to next treatment may be satisfactory surrogate end points of SAFTI in WM.


Subject(s)
Waldenstrom Macroglobulinemia/pathology , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Combined Modality Therapy , Disease Progression , Female , Humans , Male , Middle Aged , Prognosis , Proportional Hazards Models , Risk Factors , Rituximab/therapeutic use , Survival Analysis , Treatment Outcome , Vidarabine/analogs & derivatives , Vidarabine/therapeutic use , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/mortality
2.
Am J Hematol ; 90(11): 1055-9, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26284823

ABSTRACT

Lenalidomide is manageable and effective in multiple myeloma, particularly in elderly patients. Surprisingly, the combination of lenalidomide with rituximab produced clinically significant anemia at 25 mg/day for 21/28 days, the highest possible dose, in Waldenström's Macroglobulinemia (WM). We aimed to determine the maximum tolerated dose (MTD) of single agent lenalidomide and determine its impact on WM. RV-WM-0426 is a multicenter dose escalation open label phase 1/2 study of lenalidomide in relapsed/refractory WM (RRWM). Lenalidomide was given orally 21/28 days per cycle for 1 year, at escalated dose of 15 to 20 mg during phase 1 to determine the MTD; the phase 2 part was conducted at the MTD. Seventeen RRWM patients were included. The MTD was established at 15 mg/day 21/28. By ITT analysis, the overall response rate was 29%. With a median follow-up of 36 months, median TTP was 16 months (95% CI 5.5-26), the 5-year OS was 91%. The most frequent adverse events ≥ grade 3 at 15 mg were 14% anemia and 43% neutropenia. The MTD of lenalidomide is 15 mg/day 21/28 days in RRWM. Lenalidomide is active in the treatment of RRWM and the safety profile appears manageable. Future studies may look into combinations of lenalidomide and continuous dosing.


Subject(s)
Antineoplastic Agents/administration & dosage , Immunologic Factors/administration & dosage , Thalidomide/analogs & derivatives , Waldenstrom Macroglobulinemia/drug therapy , Administration, Oral , Aged , Aged, 80 and over , Anemia/chemically induced , Anemia/pathology , Antineoplastic Agents/adverse effects , Drug Administration Schedule , Drug Dosage Calculations , Female , Humans , Immunologic Factors/adverse effects , Lenalidomide , Male , Maximum Tolerated Dose , Middle Aged , Neutropenia/chemically induced , Neutropenia/pathology , Recurrence , Survival Analysis , Thalidomide/administration & dosage , Thalidomide/adverse effects , Treatment Outcome , Waldenstrom Macroglobulinemia/mortality , Waldenstrom Macroglobulinemia/pathology
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