The humanized monoclonal antibody apolizumab (Remitogen, Hu1D10), directed
against a polymorphic determinant of HLA-DR expressed on normal and malignant B
cells, is capable of inducing antibody-dependent cellular cytotoxicity,
complement-mediated lysis, and direct apoptosis of lymphoma cell lines (Int J
Cancer 93:556-565, 2001).
Results of a phase I dose escalation trial in 20
B-cell lymphoma patients reported four of eight patients with follicular
lymphoma treated with weekly infusions achieving durable responses (partial
responses or unconfirmed complete responses [Proc Am Soc Clin Oncol 20:284a,
2001]). The median time to response was 106 days, with continued remission more
than 400 days following antibody treatment. For this reason a phase II,
multicenter, open-label, randomized study in patients with relapsed or
refractory follicular, small lymphocytic, or marginal zone/mucosa-associated
lymphoid tissue (MALT) B-cell lymphoma was initiated to further determine safety
and efficacy in this population at two dose levels of apolizumab.
Patients are randomized to receive apolizumab infusions at 0.5 mg/kg or 1.5
mg/kg, once weekly for 4 consecutive weeks. Tumor response is evaluated at weeks
4 and 12 following the last apolizumab infusion, every 3 months thereafter for
the first year and every 6 months for the second year or until disease
progression occurs. A total of 60 patients will be enrolled. To date, 31 of 51
patients screened were found to have tumors that express the 1D10 antigen; 21 of
these patients have been treated with apolizumab to date.
The median patient age is 64 years (range: 53-79 years), including 13 males
and 18 females; median number of prior treatments is 3 (range: 1-6). Currently
enrolled patients have the following histologies: follicular small cell (n = 5),
follicular mixed cell
(n = 9), follicular large cell (n = 1), small lymphocytic (n = 5), and marginal
zone (n = 1) lymphoma.
Treatment has been generally well tolerated. To date, all patients have
received all scheduled infusions without treatment delay. Adverse events,
(primarily infusion-related grade 1/2) include urticaria, pruritis, angioedema,
fever, chills, hypotension, dyspnea, nausea, headache, and fatigue. One patient
experienced a grade 3 infusion syndrome during the first dose consisting of
hypotension, hypoxia, and dyspnea, and required overnight hospitalization.
Symptoms reversed with supportive care and this patient went on to receive all
four infusions. Another patient had 24 to 48 hours of facial and peripheral
angioedema, urticaria, and pruritus after each infusion, resistant to
antihistamines. Infections observed to date include one episode of oral
candidiasis and two episodes of herpes zoster.
CONCLUSION: Response data will be available with further follow-up.