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

  • 2-year OS was 95% for R-CHEMO vs 86% for CHEMO alone (p<0.05)3
  • Median of primary endpoint of time to treatment failure not reliably estimated (55% risk reduction, p<0.05)3

RITUXAN in combination with CHOP chemotherapy for DLBCL

  • Detailed safety data collection 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%)
  • 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, neutropenia, and anemia

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., 2013.

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

BOXED WARNINGS

WARNING: FATAL INFUSION REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

  • 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. Monitor patients closely. Discontinue RITUXAN infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion reactions
  • Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving RITUXAN
  • Hepatitis B Virus (HBV) Reactivation: HBV reactivation can occur in patients treated with RITUXAN, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with RITUXAN. Discontinue RITUXAN and concomitant medications in the event of HBV reactivation
  • Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving RITUXAN

Warnings and Precautions

Tumor Lysis Syndrome

  • Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, some fatal, can occur within 12−24 hours after the first infusion of RITUXAN in patients with NHL. A high number of circulating malignant cells (≥25,000/mm3) or high tumor burden, confers a greater risk of TLS. Administer aggressive intravenous hydration and anti hyperuricemic therapy in patients at high risk for TLS

Infections

  • Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of RITUXAN-based therapy. Discontinue RITUXAN for serious infections and institute appropriate anti infective therapy

Cardiovascular

  • Discontinue infusions for serious or life threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of RITUXAN for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina

Renal

  • Severe, including fatal, renal toxicity can occur after RITUXAN administration in patients with NHL. Monitor closely for signs of renal failure and discontinue RITUXAN in patients with a rising serum creatinine or oliguria

Bowel Obstruction and Perforation

  • Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving RITUXAN in combination with chemotherapy. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur

Immunization

  • The safety of immunization with live viral vaccines following RITUXAN therapy has not been studied and vaccination with live virus vaccines is not recommended

Laboratory Monitoring

  • Obtain complete blood counts (CBC) prior to each RITUXAN course

Additional Important Safety Information

  • The most common Grade 3 or 4 adverse reactions in clinical trials of NHL and CLL were infusion reactions, neutropenia, leukopenia, anemia, thrombocytopenia, and infections. Additionally, lymphopenia and lung disorder were seen in NHL trials; and febrile neutropenia, pancytopenia, hypotension, and hepatitis B were seen in CLL trials
  • The most common adverse reactions (incidence ≥25%) in clinical trials of NHL and CLL were infusion reactions. Additionally, fever, lymphopenia, chills, infection, and asthenia were seen in NHL trials; and neutropenia was seen in CLL trials
  • Pregnancy: Category C. There are no adequate and well-controlled studies of rituximab in pregnant women

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.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.

You may also report side effects to Genentech at (888) 835-2555.