Split-Dose R-CHOP for Older Adults with Diffuse Large B-cell Lymphoma

Inclusion Criteria

• Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial
• All patients age >= 75 years and patients aged 70-74 years who are determined to be unfit or frail by Cumulative Illness Rating Scale for Geriatrics (CIRS-G scale) * For patients aged 70-74 years: CIRS-G score with 5-8 comorbid conditions scored 2 or >=1 comorbidity scored 3-4
• Newly diagnosed, untreated, biopsy proven CD20 positive DLBCL (including high grade B-cell lymphoma & T-cell/histiocytic rich large B-cell lymphoma). Patients with discordant bone marrow (i.e. involved by low-grade/indolent non-Hodgkin lymphoma [NHL]) are eligible. Patients with transformed DLBCL from underlying low-grade disease are eligible. Patients with composite DLBCL and concurrent low-grade lymphoma are eligible * Copy of pathology report must be sent to coordinating site to confirm diagnosis for eligibility * Patients with prior treatment for low grade NHL with non-anthracycline based regimens are eligible
• Measurable disease by PET/CT or bone marrow (BM) biopsy prior to enrollment
• Left ventricular ejection fraction >= 50% by resting echocardiography or resting multigated acquisition (MUGA) scan
• Karnofsky performance score >= 50
• Ann Arbor stage II bulky, III, or IV disease
• Minimum life expectancy greater than 3 months
• Negative human immunodeficiency virus (HIV) test
• For patients with hepatitis B virus antigen (HbsAg) or core antibody (HbcAb) seropositivity, patients must have a negative hepatitis B (Hep B) viral load and an appropriate prophylaxis plan must be in place during chemotherapy therapy treatment. For all patients that have hep B core antibody positive, they should take entecavir prophylaxis (0.5 mg PO daily) until 1 year from completion of chemotherapy. Hep B viral load should be checked on these patients prior to starting chemotherapy and every 3 months thereafter if initial hep B viral load is negative (+/- 1 week if chemotherapy cycle is delayed). If Hep B viral load is positive, hepatology or identification (ID) referral is recommended, and hepatitis B virus (HBV) viral load should be checked monthly
• For patients with hepatitis C Ab (HbcAb) positivity, a viral load must be checked and be negative for enrollment
• Intrathecal chemotherapy for central nervous system prophylaxis only can be given at the discretion of the primary oncologist

Exclusion Criteria

• History of previous anthracycline exposure
• Central nervous system (CNS) or meningeal involvement at diagnosis
• Creatinine clearance =< 25 mL/min by Cockcroft-Gault
• Poor hepatic function, defined as total bilirubin concentration greater than 3.0 mg/dL or transaminases over 4 times the maximum normal concentration, unless these abnormalities are felt to be related to the lymphoma
• Pulmonary dysfunction defined as > 2 L of oxygen required by nasal cannula to maintain peripheral capillary oxygen saturation (SpO2) >= 90% unless felt to be related to underlying lymphoma
• Myocardial Infarction within 6 months of enrollment
• Active, uncontrolled infectious disease
• Known concurrent bone marrow malignancies (e.g. myelodysplastic syndrome) or poor bone-marrow reserve, defined as neutrophil count less than 1.5 x 10^9/L or platelet count less than 100 x 10^9/L, unless caused by bone-marrow infiltration with lymphoma
• History of a second concurrent active malignancy or prior malignancy which required chemotherapy treatment within the preceding 2 years
• Treatment with any investigational drug within 30 days before the planned first cycle of chemotherapy
• Unable or unwilling to sign consent