Long Term Outcome Following Treatment Failure of FCR Chemoimmunotherapy as Initial Therapy for Chronic Lymphocytic Leukemia.
Authors: Keating Michael J. , Wierda William G. , Tam Constantine S. , Lynn Alice , O'Brien Susan , Lerner Susan , Kantarjian Hagop M. 
Published: October 2019

Abstract
Abstract 2381
Poster Board II-358
The natural history of patients (pts) who fail or relapse after chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) has not been established. Three hundred pts received FCR as initial therapy for progressive or advanced chronic lymphocytic leukemia (CLL) (Tam CS; Blood 112(4):975-980, 2008). Fifteen (5%) pts failed to respond, 72% achieved a CR and 22% a PR. Treatment failure occurred in 18 pts because of the development of AML, MDS or Richter's transformation and there were 15 deaths in remission (infection (7), cancer (6), or cardiac events (2)). Fourteen relapsed pts have not received therapy and are considered to be “watch and wait.”
One hundred and twelve pts have received therapy. A large variety of treatment programs were administered at time of relapse during the ten years of the study. The most commonly used were FCR-like regimens (33) with or without lumiliximab or bevacizumab, FCR + alemtuzumab (CFAR) 9 pts, rituximab-based regimens (28) +/- GMCSF or steroids, Campath-based regimens (16) +/- rituximab, and a variety of other phase I and miscellaneous salvage treatments. 79 pts received salvage therapy at M. D. Anderson Cancer Center (MDACC) and the 33 others in their local community. 17 patients (16%) achieved a CR and 46 a PR (4%). CR rates were 15% for FCR, 56% for CFAR, 4% for rituximab regimens, 31% for alemtuzumab regimens and 4% for other regimens. While higher CR rates were noted in alemtuzumab regimens, no difference in time-to-treatment failure or survival was noted. The median overall survival was 33 months with a 40% five-year survival rate. A number of characteristics shown in Table 1 associated with complete remission and overall response rate.
Outcome of 1st Salvage – FCR Relapsed/Refractory (112 pts) Characteristic Value Patients %CR %OR Med Surv (Mths) Age / years <65 79 18 57 42 .04 ≥65 33 9 55 22 Beta-2 microglobulin (mg/L) <4 50 24* 60 46 .005 ≤4 39 8 51 17 Rai Stage 0 - III 50 24 68 41 .01 IV 35 11 40 15 Time to Rx Failure (Mths) <36 43 12 42 12 <.0001 ≥36 69 17 65 44 FISH 17p 11 9 18 11 .002 11q- 26 23* 65 41 Other 24 4 46 NR * p<0.05
All of the listed characteristics were significantly associated with survival. Abnormalities in 17p detected by FISH, short time to treatment failure, and Rai stage IV were associated with the worst prognosis. 31 pts received an allogeneic stem cell transplant (SCT) either at MDACC or elsewhere. The SCT was usually done as second or subsequent salvage therapy with a five-year survival fraction of approximately 35%.
More than half the patients who relapsed after FCR can achieve at least a partial response with salvage therapy. The optimum treatment for this group of pts is ill-defined. Preparation for and consideration of allogeneic stem cell transplantation should be considered for all pts who achieved only a partial response after salvage therapy.

Disclosures:
Keating: Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wierda:Genentech: Consultancy, Honoraria; Genzyme: Research Funding. O'Brien:Genentech: Research Funding; Biogen Idec: Research Funding.