Loncastuximab Tesirine in Combination with Rituximab for the Treatment of Relapsed/Refractory Follicular Lymphoma

Inclusion Criteria

• Men and women >= 18 years of age
• Patients must have histologic confirmation of FL (grade 1, 2 and 3A) defined by the World Health Organization (WHO) classification. Note: Participants who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy
• Patients with relapsed or refractory FL previously treated with >= 1 line of systemic therapy having >=1 Groupe d’Etude des Lymphomes Folliculaires (GELF) criteria for therapy, POD24, or second relapse
• Baseline FDG-PET/CT scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites. Patients should have at least one measurable site of disease per Lugano classification
• Patient should have >= 1 Groupe d’Etude des Lymphomes (GELF) criteria for treatment initiation) * Involvement of >= 3 nodal sites, each with diameter of >= 3 cm * Any nodal or extranodal tumor mass with a diameter of >= 7 cm * B symptoms (fever >= 38 degrees Celsius of unclear etiology, night sweats, weight loss > 10% within the prior 6 months) * Risk of local compressive symptoms that may result in organ compromise * Splenomegaly or splenic lesion without splenomegaly * Leukopenia (leukocytes < 1000/mm^3) * Leukemia (> 5.000 lymphoma cells/mm^3) * Bone lesions detected on FDG-PET/CT will be also consider an indication for treatment
• Progression or relapse within 24 months (POD24) of frontline treatment in patients previously treated with >= 1 line of systemic therapy
• Second FL relapse/progression after >= 1 line of systemic therapy. These patients will be eligible independently of GELF criteria and POD24
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Life expectancy of greater than 6 weeks
• Absolute neutrophil count >=1000/mm^3 (unless due to lymphoma involvement of the bone marrow or spleen)
• Platelets >= 100,000/mm^3 or >= 60,000/mm^3 in case of bone marrow involvement by lymphoma
• Hemoglobin >= 10 g/dL or >= 8 g/dL in case of bone marrow involvement by lymphoma
• Total bilirubin < 1.5 x within normal institutional limits (unless due to lymphoma involvement of liver or a known history of Gilbert’s disease)
• Gamma-glutamyl transpeptidase (GGT)/aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
• Creatinine within normal institutional limits, or creatinine clearance >= 30 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (unless due to lymphoma)

Exclusion Criteria

• FL grade 3B or transformed FL
• > 6 lines of systemic immunochemotherapy for treatment of FL
• Patients with clinically significant pleural effusions and/or ascites requiring drainage or associated with shortness of breath
• Patients receiving any other investigational agents
• Patients with known central nervous system involvement of lymphoma
• Uncontrolled intercurrent illness such as: history of myocardial infarction (MI) in the last 6 months, congestive heart failure New York Heart Association (NYHA) Class III-IV, uncontrolled or symptomatic arrhythmia, stroke in last 6 months, liver cirrhosis, and autoimmune disorder requiring immunosuppression or long-term corticosteroids (> 10 mg daily prednisone equivalent)
• Breastfeeding or pregnant women
• Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody will need a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.) Hepatitis C antibody positive patients are eligible if PCR is negative. Hepatitis B core antibody (+) patients without evidence of HBsAg or Hep B PCR (+) are eligible with appropriate hepatitis B reactivation prophylaxis
• History of human immunodeficiency virus (HIV) infection. Note: HIV screening test is optional
• Patients with impaired decision-making capacity