Results of a Prospective Phase II Trial of Limited and Extended Rituximab Treatment in Nodular Lymphocyte Predominant Hodgkin’s Disease (NLPHD).

Background: NLPHD represents a unique clinical entity characterized by limited peripheral nodal disease, an indolent behavior with a frequent relapse pattern following radiotherapy or chemotherapy, and late treatment-related effects. Distinct from classical HD, the malignant cells of NLPHD are universally CD20+ and we therefore postulated that rituximab may have activity with fewer adverse effects.

Methods: In this prospective phase II trial, patients (pt) with untreated or relapsed CD20+ NLPHD and measurable disease were eligible to receive four weekly doses of rituximab at 375 mg/m2. Restaging studies after completion of all treatment were performed at 1, 3 and 6 months (mo), and every 6 mo thereafter to progression. Endpoints were estimated response rate, freedom from progression (FFP) and safety. We previously reported that FFP was less than 1 year despite the fact that all patients responded to a limited, weekly × 4 treatment (

Results: Pt received limited (n=23, 12 previously untreated) or extended (n=16, 9 previously untreated) rituximab. Median age at treatment was 44 yr (17–71) with 26 males. Among 21 previously untreated pt, stages were I (6), II (8), or III (7). Median follow-up is 60 months (mo) for all pt, 72 mo for limited and 30 mo for extended treatment pt. Treatment-related adverse events were minimal and no grade 3 or 4 toxicities were reported. All but 1 pt responded (OR 97%) with CR/CRu in 27 (69%), and PR in 11 (28%) and SD in 1 (3%). CR/CRu was achieved in 56% limited and 88% extended rituximab pt (p=0.08). No difference was observed in previously treated v untreated pt. To date, 17 progressions (15 limited, 2 extended rituximab) have been recorded. Median FFP was 24 mo for limited and not reached for extended rituximab (p=0.03). FFP at 30 months was estimated at 52% for limited rituximab and 88% for extended rituximab pt. Four pt transformed to large cell lymphoma (one after multiple relapse treatments). Three deaths occurred, one each due to colon cancer, acute leukemia (pt heavily pre-treated with radiation and MOPP), and large cell lymphoma. For all 38 pt, median follow-up from diagnosis is 7.5 yr (range (<1–38) and survival from diagnosis is estimated at 97% at 10 yr and 85% at 20 yr.

Conclusions: Rituximab is an effective treatment in de novo or recurrent NLPHD that may be associated with fewer adverse effects than conventional therapy. FFP is prolonged with an extended treatment but additional follow-up is needed to better assess the duration of benefit.