MInT Trial

RITUXAN+CHEMO significantly prolonged OS in younger DLBCL patients

MInT TRIAL DESIGN: R-CHEMO ×6 VS CHEMO ×61

Chart: MInT Trial Design: R-Chemo x6 vs Chemo x6
  • CHEMO=CHOP every 3 weeks, CHOEP (CHOP+etoposide) every 3 weeks, MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin) biweekly, or PMitCEBO (prednisolone, mitoxantrone, cyclophosphamide, etoposide, bleomycin, and vincristine) biweekly. R=RITUXAN 375 mg/m2 every 3 weeks for 6 cycles, beginning on the first day of chemotherapy.2
  • MInT=MabThera® (Rituximab) International Trial; OS=overall survival; DLBCL=diffuse large B-cell lymphoma; IPI=International Prognostic Index; CHOP=cyclophosphamide, doxorubicin, vincristine, and prednisone.

MInT: YOUNGER, LOW-RISK DLBCL PATIENTS1

Baseline patient characteristics R-CHEMO
(n=413) 		CHEMO
(n=410)
Age range (years) 18-60 18-60
Median age 47 47
Elevated LDH (>1×ULN) 30% 29%
Ann Arbor Stage I/II III/IV 72%
27% 		72%
28%
ECOG performance status 0-1 2-3 100%
<1% 		99%
<1%
Bulky disease (>10 cm) 50% 48%
Extranodal involvement (≥2) 33% 35%
IPI score* <2 ≥2 100%
0% 		99%
<1%
  • *In the MInT trial of younger adults, an age-adjusted IPI was used, which ranged from 0 to 3 and was derived by assigning 1 point for each of the following risk factors: Ann Arbor Stage III or IV, ECOG performance status ≥2, and elevated LDH. Per the protocol, patients were to have an IPI score of <2.
  • LDH=lactate dehydrogenase; ULN=upper limit of normal; ECOG=Eastern Cooperative Oncology Group.

R-CHEMO provided a significant overall survival advantage in DLBCL

  • 1.8-year OS was 95% for R-CHEMO vs 86% for CHEMO alone (p<0.05)3
  • Significant improvement in the primary endpoint of time to treatment failure at 1.8-year follow-up (55% risk reduction, p<0.05)3

Safety for RITUXAN in combination with CHOP chemotherapy for DLBCL

  • Detailed safety data collection in these trials was primarily limited to Grade 3 and 4 adverse reactions and serious reactions. In studies of elderly patients with DLBCL, the following adverse reactions, regardless of severity, were reported more frequently (≥5%) in patients ≥60 years of age receiving R-CHOP as compared with CHOP alone: pyrexia (56% vs 46%), lung disorder (31% vs 24%), cardiac disorder (29% vs 21%), and chills (13% vs 4%)
  • In one of the studies of elderly patients, GELA LNH 98-5, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs 1.0% for CHOP)
  • The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs 7%) and lung disorder (6% vs 3%). Other Grade 3 or 4 adverse reactions reported more frequently among patients receiving R-CHOP were viral infection (GELA LNH 98-5 study), neutropenia (GELA LNH 98-5 and MInT studies), and anemia (MInT study)

References:
  1. Data on file, Genentech, Inc.
  2. Pfreundschuh M, Trümper L, Österborg A, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7:379-391.
  3. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2012.

Indications

RITUXAN® (Rituximab) is indicated for the treatment of patients with:

  • Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
  • Previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to RITUXAN in combination with chemotherapy, as single-agent maintenance therapy
  • Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy
  • Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens
  • Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC)

RITUXAN is not recommended for use in patients with severe, active infections.

Important Safety Information

WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)

Infusion Reactions: RITUXAN administration can result in serious, including fatal, infusion reactions. Deaths within 24 hours of RITUXAN infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Carefully monitor patients during infusions. Discontinue RITUXAN infusion and provide medical treatment for Grade 3 or 4 infusion reactions.

Tumor Lysis Syndrome (TLS): Acute renal failure requiring dialysis with instances of fatal outcome can occur in the setting of TLS following treatment of non-Hodgkin's lymphoma (NHL) with RITUXAN monotherapy.

Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving RITUXAN.

Progressive Multifocal Leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving RITUXAN.

Warnings and Precautions

RITUXAN has also been associated with other serious and/or fatal adverse reactions. These include

  • hepatitis B reactivation with fulminant hepatitis; hepatic failure resulting in death
  • serious, including fatal, bacterial, fungal, and new or reactivated viral infections
  • cardiovascular events, including serious or life-threatening cardiac arrhythmias
  • severe, including fatal, renal toxicity
  • abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving RITUXAN in combination with chemotherapy

Additional Important Safety Information

  • The most frequent Grade 3 or 4 adverse reactions observed in NHL were cytopenias, including lymphopenia. The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with NHL were infusion reactions, fever, lymphopenia, chills, infection, and asthenia. The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion. These infusion reactions typically resolved with slowing or interruption of the infusion and with supportive care
  • The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with CLL were infusion reactions and neutropenia. Infusion-related adverse reactions occurring during or within 24 hours of the start of infusion included nausea, pyrexia, chills, hypotension, vomiting, and dyspnea
  • Most CLL patients treated with R-FC experienced at least one Grade 3 or 4 adverse reaction. The Grade 3 or 4 adverse reactions observed more frequently with R-FC compared with FC alone were neutropenia, leukopenia, febrile neutropenia, thrombocytopenia, infusion reactions, pancytopenia, hypotension, and hepatitis B
  • In clinical trials, CLL patients 70 years of age or older who received R-FC had more Grade 3 and 4 adverse reactions compared with younger CLL patients who received the same treatment

For additional safety information, please see the full prescribing information, including BOXED WARNINGS and Medication Guide.

Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion.