Campath-1H Therapy in 29 Patients With Refractory CLL: ‘True’ Complete Remission is an Attainable Goal

OncologyONCOLOGY Vol 14 No 3
Volume 14
Issue 3

A total of 29 patients with chronic lymphocytic leukemia (CLL) refractory to therapy, including purine analogs in all cases, were treated with the monoclonal antibody, Campath-1H. (A 30-mg dose of Campath-1H was administered intravenously

A total of 29 patients with chronic lymphocytic leukemia (CLL) refractory to therapy, including purine analogs in all cases, were treated with the monoclonal antibody, Campath-1H. (A 30-mg dose of Campath-1H was administered intravenously [IV] three times weekly until maximal response occurred.) Response to therapy

was analyzed by conventional techniques, as well as by minimal residual disease (MRD) four-color flow cytometry, which we have previously demonstrated to be highly sensitive (< 1 in 10,000 cells). The median follow-up is 14.5 months (range, 1 to 36 months).

Of the 29 patients, 17 (59%) patients responded to therapy, with 10 (34%) achieving a complete remission (CR) according to National Cancer Institute (NCI) criteria. Of these 10 patients, 5 had CLL detectable by flow cytometry and the other 5 had CLL undetectable by any technique. The patients who responded to Campath-1H had a better event-free survival than nonresponders (median survival, 17 vs 4 months) and a longer overall survival. Significant lymphadenopathy at the time of Campath-1H therapy predicted for a worse response: 14 of 17 patients without lymphadenopathy responded, as compared with 3 of 12 patients with lymphadenopathy.

Peripheral blood stem-cell mobilization and collection did not appear to be affected by Campath-1H therapy. Nine responding patients proceeded to peripheral blood stem-cell transplantation (PBSCT), with an improvement in remission status in four of seven assessable patients and in two of these, the response converted to no detectable CLL (MRD negative).

Of the nine responding patients who underwent transplantation, eight are alive at a median of 14 months (range, 1 to 29 months) post-PBSCT. One has required further therapy. The remaining patient died on the 14th day after transplantation due to a complication of the transplant procedure.

Another patient who did not respond to Campath-1H and had progressive disease underwent transplantation, had a transient partial response, and died of progressive disease at 6 months post-PBSCT.

We have used the highly sensitive, quantitative MRD flow analysis to follow patients after Campath-1H therapy. Two of the five patients with no detectable disease developed detectable disease within 6 months of therapy but have not yet progressed clinically. The remaining three patients have no detectable CLL on repeated analyses (21, 23, and 34 months following Campath).

Repeated use of MRD flow assay post–Campath-1H allows for estimation of disease doubling time and prediction of disease progression. In six responding patients with detectable CLL, the median doubling time was 121 days (range, 54 to 244 days) and was predictive of the time of disease progression. Three of these patients have subsequently been retreated with Campath-1H, with two achieving a further response.

CONCLUSION: Campath-1H is an effective therapy for patients with refractory CLL, in particular, those without significant lymphadenopathy. Repeated analysis with a highly sensitive MRD flow assay identifies a group of patients who attain an apparent “true” complete response, and, in a proportion of these patients, the remission is protracted (34+ months). PBSCT is a feasible procedure in patients with detectable residual disease following Campath therapy and often results in an improvement in depth of remission.

Click here for Dr. Bruce Cheson’s commentary on this abstract.

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Prospective, Randomized, Controlled Study of Zevalin Radioimmunotherapy Compared to Rituximab Immunotherapy for B-Cell, Non-Hodgkins Lymphoma: Interim Results
IOM Medical Error Estimates Questioned, But Legislation Considered
Less Toxic Therapies for Hodgkin’s Disease May Reduce Secondary Cancers
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Iodine-131 Tositumomab for Patients With Transformed, Low-Grade Non-Hodgkin’s Lymphoma: Overall Clinical Trial Experience
Survival Rates Significantly Worse For African-Americans With Endometrial Cancer
Rituximab Has Significant Activity in Patients With Chronic Lymphocytic Leukemia
Responders to Rituximab Show Continued Tumor Regression Over Time and a Progression-Free Survival That Correlates With Response Classification
PhRMA Criticizes FDA’s Proposed Rule on Antibiotic Approvals
Phase II Study of Rituximab in Combination With CHOP in Patients With Previously Untreated Intermediate- or High-Grade Non-Hodgkin’s Lymphoma
New Antibiotic Effective in Treating Gram-Positive Bacteremia
Reduced-Dose Zevalin Radioimmunotherapy for Relapsed or Refractory B-Cell Non-Hodgkin&#146;s Lymphoma Patients With Preexisting Thrombocytopenia: Report of Interim Results of a Phase II Trial
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