New Agents and Strategies in CLL Treatment

Abstract

Fludarabine Monophosphate (FLU) is an adenosine analogue with a high-level of anti-leukemic activity in patients (pts) with CLL. FLU (25–30 mg/m²/day × 5 every 4 weeks) was given to 78 previously treated pts with CLL. The overall response rate was 58% (CR 11%, nodular CR 26%, PR 21%). Subsequently, prednisone (P, 30 mg/m²/day × 5) was added to the FLU regimen and administered to 169 pts. The response rate, up to this time, was similar to the FLU regimen 52% (CR 12%, nodular CR 28%, PR 12%). The major toxicity was febrile episodes which occurred in one course in 5 for both groups of pts. The median survival was also similar in both groups (FLU 74 weeks and FLU + P 103 weeks). Thus, no advantage was noted with the addition of P to FLU. FLU and FLU + P have been administered to 36 pts and 62 pts respectively who have had no prior treatment. The response rate for FLU was 83% (CR 39%, nodular CR 36%, PR 8%) and FLU + P was 82% (CR 29%, nodular CR 34%, PR 19%). Several of the FLU + P group developed persistent thrombocytopenia despite a good anti-leukemic response. The rates of decrease of the circulating and marrow lymphocyte counts were similar for the FLU and FLU + P groups. No survival difference has been noted to date in these groups. Time to development of progressive disease in the previously treated pts FLU and FLU + P is 104 weeks and is similar for the CR and nodular CR pts 118 weeks vs. 97 weeks and for the PR pts 89 weeks. All pts appear eventually to recur. Insufficient data is available to evaluate the time to progression of the previously treated pts. Two parameter flow-cytometry for CD19 and CD5, Kappa/Lamda ratio and immunoglobulin gene rearrangement studies are able to detect residual bone marrow disease in a majority of pts with CR and nodular CR (BM lymphocytes <30%). As relapse appears to be inevitable in the previously treated group who respond, post-remission therapy will include autologous bone marrow transplantation for pts <60 years of age and recombinant alpha-Interferon for pts >60 years of age. Post-remission therapy for the previously untreated responders will not be given to allow an estimate of the unmaintained time to progression. Bone marrow will be stored in first remission for future use, if the pts recur. Combination therapy studies utilizing FLU combined with Ara-C or Doxorubicin are being conducted.

Key Words:

• New agents
• Strategies in CLL