Commentary on Abstracts #3153, #3592, #3168, #3170, #704, #2214, #3275, #1086, #2560, and #3264

Rituximab is also being explored in other lymphoid malignancies. Some of the most interesting data are in patients with CD20-positive Hodgkin’s disease (abstract #3153). The Stanford group (abstract #3592) reported on 13 patients. Of the 9 who were assessable for response, there were 6 CRs and 3 PRs with a single relapse at 6 months. The German Hodgkin’s group reported on 6 patients, all of whom had failed at least one prior treatment regimen. Of the 5 with lymphocyte-predominant Hodgkin’s disease, there were 4 CRs and 1 PR; the patient with classical Hodgkin’s disease also attained a CR. Lower response rates appear to be achievable in patients with classical Hodgkin’s disease (abstract #3168), with 1 CR and 2 PRs in 18 patients with nodular sclerosis histology, 13 of whom had progressed after stem cell transplantation. Clearly, this agent should be studied as part of a multidrug regimen in the treatment of this disease.

Coiffier et al (Blood 92:1927-1932, 1998) have previously demonstrated activity for rituximab in patients with mantle cell lymphoma, although responses were brief without further therapy. Romaguera et al (abstract #3170) added the antibody to their effective hyper CVAD (cyclophosphamide, vincristine, doxorubicin [Adriamycin], dexamethasone) regimen (Khouri et al: J Clin Oncol 16:3803-3809, 1998) and presented their data from an ongoing trial in 43 patients. The CR rate was 90%, but longer follow-up is needed to assess the durability of responses in this population. Treon et al (abstract #704) treated 19 multiple myeloma patients whose bone marrow cells were CD20 positive, with a single partial response.

Using the standard dose and schedule of administration, rituximab has exhibited relatively limited single-agent activity in small lymphocytic lymphoma/chronic lymphocytic leukemia (Piro et al: Proc Am Soc Clin Oncol 18:14a[abstract #49], 1999; Nguyen et al: Eur J Haematol 62:76-82, 1999; Maloney et al: Blood 90:2188-2195, 1997). Nevertheless, in vitro and early clinical data suggest the potential for the antibody to sensitize lymphoma cells to the effects of chemotherapy. As a result, rituximab is being incorporated into multiagent regimens with promising results.

Keating et al (abstract #2214) built on their prior institutional experience using the combination of fludarabine and cyclophosphamide (O’Brien et al: Int J Hematol 64:S56[abstract #214], 1996) by adding rituximab. Of the 35 patients evaluable after six courses, there were 57% CRs and a response rate of 94%; for those who had completed only three courses, responses occurred in 81%, with 14% CRs. Major infections were uncommon (3%), with no opportunistic organisms. Impressive data were also reported for patients with previously treated chronic lymphocytic leukemia using this same regimen (abstract #3275).

Based on its B-cell-depleting properties, rituximab as a single agent or in combination with immunosuppressive chemotherapy drugs has been used to treat nonmalignant conditions such as immune thrombocytopenic purpura and autoimmune hemolytic anemia (Hegde et al: Proc Am Soc Clin Oncol [in press], 2001; Perrota and Abuel: Blood 92:88b[abstract #3360], 1998; abstracts #1086, #2560, #3264), with encouraging success in many patients who failed conventional therapies.