90-minute infusion for previously untreated DLBCL and follicular NHL patients in Cycles 2-8

The 90-minute infusion rate means some of your patients may be able to receive RITUXAN therapy in half the average time of the standard infusion.^1-3

RITUXAN 375 mg/m² INFUSION TIME FOR APPROPRIATE PATIENTS^1-3

• *For standard infusions in Cycles 2-8, initiate at a rate of 100 mg/hr. In the absence of infusion toxicity, increase rate by 100 mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr.¹

The faster infusion rate can be administered to patients who^1-3

• • Have previously untreated DLBCL or follicular lymphoma, receiving R-CHOP or R-CVP, respectively
  • Are ≥18 years of age
  • Have an ECOG PS 0-2
  • Have a circulating lymphocyte count <5,000/µL at the start of Cycle 2
  • Did not experience any infusion-related serious adverse event (SAE) or Grade 3/4 infusion-related reaction (IRR) in Cycle 1
  • Do not have significant cardiovascular disease^†

• Patients in Stage 3 or 4 of DLBCL and follicular lymphoma were included in the RATE trial^2,3
• All patients were premedicated with acetaminophen and an antihistamine prior to RITUXAN administration^1-3
• Patients had a glucocorticoid component of R-CHOP or R-CVP administered prior to RITUXAN. No other glucocorticoids were allowed^1-3

• ^†Per protocol, clinically significant cardiovascular disease is defined as uncontrolled hypertension, myocardial infarction, or unstable angina; New York Heart Association (NYHA) Classification Grade II or greater congestive heart failure; a ventricular arrhythmia requiring medication within 1 year prior to Day 1; or NYHA Grade II or greater peripheral vascular disease on Day 1.³

The infusion rate for 90-minute RITUXAN in appropriate patients is:

• 20% of the total dose over the first 30 minutes (75 mg/m²)^1-3
• 80% of the total dose over the following 60 minutes (300 mg/m²)^1-3
• If the 90-minute infusion is tolerated in Cycle 2, the same rate can be used when administering the remainder of the treatment regimen (through Cycle 6 or 8)¹

• DLBCL=diffuse large B-cell lymphoma; NHL=non-Hodgkin's lymphoma; R=RITUXAN; CHOP=cyclophosphamide, doxorubicin, vincristine, and prednisone; CVP=cyclophosphamide, vincristine, and prednisone; ECOG PS=Eastern Cooperative Oncology Group performance status.

In the treatment of previously untreated patients with DLBCL or follicular lymphoma receiving R-CHOP or R-CVP, respectively

 

Is your patient right for the 90-minute RITUXAN infusion?1-3
Previously untreated patients with DLBCL or follicular lymphoma who were scheduled to receive RITUXAN 375 mg/m2 plus CHOP or CVP chemotherapy, respectively Age ≥18 years ECOG performance status 0-2 No significant cardiovascular disease (ie, uncontrolled hypertension myocardial infarction, unstable angina)* Standard infusion in Cycle 1 produced no incidences of Grade 3 or 4 IRRs or SAEs Circulating lymphocyte count of <5,000/µL at the start of Cycle 2

• *Per protocol, clinically significant cardiovascular disease is defined as uncontrolled hypertension, myocardial infarction, or unstable angina; New York Heart Association (NYHA) Classification Grade II or greater congestive heart failure; a ventricular arrhythmia requiring medication within 1 year prior to Day 1; or NYHA Grade II or greater peripheral vascular disease on Day 1.³

• All criteria must be checked for a patient to be considered an appropriate candidate for 90-minute RITUXAN infusion

DLBCL=diffuse large B-cell lymphoma; NHL=non-Hodgkin's lymphoma; R=RITUXAN; CHOP=cyclophosphamide, doxorubicin, vincristine, and prednisone; CVP=cyclophosphamide, vincristine, and prednisone; ECOG=Eastern Cooperative Oncology Group; IRR=infusion-related reaction; SAE=serious adverse event.

Demonstrated safety profile with a 90-minute infusion in Cycles 2-8

The primary endpoint of the RATE (U4391g) trial was the incidence of Grade 3 or 4 IRRs in Cycle 2; the incidence of Grade 3 IRRs on Days 1-2 of Cycle 2 was 1.1%, with no reported incidence of Grade 4 IRRs^1-3

RATE (U4391g) TRIAL: SAFETY PROFILE IN CYCLES 1 AND 2^2,3

 

Cycle 1 Patients, n (%)	R-CHOP (n=250)	R-CVP (n=113)	Total (n=363)
AEs (any grade) at Cycle 1    Grade 3/4 AEs	230 (92.0) 89 (35.6)	104 (92.0) 22 (19.5)	334 (92.0) 111 (30.6)
IRRs at Cycle 1, Days 1-2	107 (42.8)	50 (44.2)	157 (43.3)
SAEs* at Cycle 1	29 (11.6)	7 (6.2)	36 (9.9)
Serious IRRs at Cycle 1, Days 1-2	1 (0.4)	0(0.0)	1 (0.3)

Cycle 2, Days 1-2 Patients, n (%)	R-CHOP (n=250)	R-CVP (n=113)	Total (n=363)
Total Grade 3 AEs	5 (2.0)	5 (4.4)	10 (2.8)
Total Grade 3 IRRs Rash Bronchospasm Hypersensitivlty Abdominal pain	0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)	4 (3.5) 1 (0.9) 1 (0.9) 1 (0.9) 1 (0.9)	4 (1.1) 1 (0.3) 1 (0.3) 1 (0.3) 1 (0.3)
Total Grade 4 AEs	0 (0.0)	0 (0.0)	0 (0.0)
Total Grade 4 IRRs	0 (0.0)	0 (0.0)	0 (0.0)

*SAE=a non-infusion−related event that was determined by the investigator as being life-threatening, or causing permanent disability or hospitalization, or death. Patients with infusion-related SAEs in Cycle 1 were excluded from the trial per protocol and are not included here.¹

A faster infusion rate of RITUXAN is available for appropriate patients^1-3

• Adverse events reported in patients who received a 90-minute infusion in Cycle 2 Day 1 were typical of patients treated with R-CHEMO
• No fatal IRRs or AEs on Days 1-2 of any cycle
• The discontinuation rate due to AEs seen with the faster infusion on or after Cycle 2 was 2.7%^†

^†A total of 68 patients discontinued treatment on or after Cycle 2 due to: AEs (12), death (6), disease progression (3), lost to follow-up (3), physician decision (13), or patient decision (6). Twenty-five patients withdrew for other reasons.^2,3

DLBCL=diffuse large B-cell lymphoma; NHL=non-Hodgkin's lymphoma; IRR=infusion-related reaction; R=RITUXAN; CHOP=cyclophosphamide, doxorubicin, vincristine, and prednisone; CVP=cyclophosphamide, vincristine, and prednisone; AE=adverse event; SAE=serious adverse event.

Demonstrated Results in Community and Academic Centers

• The RATE (U4391g) trial was conducted in community practices and academic centers across the country^1,2
• Patients with previously untreated DLBCL or follicular lymphoma who were scheduled to receive RITUXAN 375 mg/m² plus CHOP or CVP chemotherapy, respectively, were eligible for study participation^1-3
• Patients in Stage 3 or 4 of DLBCL and follicular lymphoma were included in the RATE trial^1,2

RATE (U4391g) TRIAL DESIGN^1-3

• *All patients received premedication with acetaminophen and an antihistamine.^1-3
• ^†Per protocol, clinically significant cardiovascular disease is defined as uncontrolled hypertension, myocardial infarction, or unstable angina; New York Heart Association (NYHA) Classification Grade II or greater congestive heart failure; a ventricular arrhythmia requiring medication within 1 year prior to Day 1; or NYHA Grade II or greater peripheral vascular disease on Day 1.¹
• ^‡SAEs that were not infusion-related did not mandate exclusion from the trial per protocol.^1,2
• ^§20% of dose administered in first 30 minutes; 80% of dose administered in next 60 minutes.^1-3
• ^||Patients received either RITUXAN plus CHOP chemotherapy or RITUXAN plus CVP chemotherapy.^1-3

• Of the 425 patients treated with RITUXAN in Cycle 1, 85% (n=363) were able to receive the 90-minute infusion of RITUXAN in Cycle 2^1-3
• Patients were eligible to receive a 90-minute RITUXAN infusion in Cycle 2 if they did not experience an infusion-related SAE or a Grade 3 or 4 IRR in Cycle 1, if they had a circulating lymphocyte count <5,000/μL, and if they did not have significant cardiovascular disease^1,3†
  • An SAE is an adverse event that was determined by the investigator as being life-threatening, or causing permanent disability or hospitalization, or death¹
  • Grade 3/4 IRRs were AEs that resulted from the faster infusion, according to NCI grading¹
• Patients received a median of 6 cycles of RITUXAN, with the majority receiving at least 6 cycles^1,2
• All patients were premedicated with acetaminophen and an antihistamine prior to RITUXAN administration^1-3
• The glucocorticoid component of the chemotherapy regimen was given to the patients prior to RITUXAN administration. No other glucocorticoids were allowed^1-3

• DLBCL=diffuse large B-cell lymphoma; NHL=non-Hodgkin's lymphoma; CHOP=cyclophosphamide, doxorubicin; vincristine, and prednisone; CVP=cyclophosphamide, vincristine, and prednisone; R=RITUXAN; ECOG PS=Eastern Cooperative Oncology Group performance status; IRR=infusion-related reaction; SAE=serious adverse event; NCI=National Cancer Institute.

Can I administer a faster infusion to Stage 3 and 4 patients?

In the RATE trial, 39% of patients had stage 3 NHL and 29% had stage 4 NHL.^1,2

Can I administer a faster infusion to patients with a high tumor burden?

For patients who were enrolled in the RATE trial, the mean measurement of the longest diameter of the largest lesion was 5.2 cm. The range was between 0 and 23 cm. Patients with a circulating lymphcyte count of >5,000/μL before Cycle 2 were excluded from the RATE study.^1,2

Can I administer a faster infusion to patients with a high lymphocyte count?

Patients with a circulating lymphocyte count of >5,000/μL before Cycle 2 were excluded from the RATE study.^1,2

How were patients on the study premedicated?

The glucocorticoid component of the chemotherapy regimen was administered before beginning RITUXAN therapy. All patients were premedicated with acetaminophen and an antihistamine prior to receiving RITUXAN, to reduce the risk of IRRs.^1-3

Can I give the 90-minute infusion to my CLL patients or follicular NHL patients who are receiving post-induction therapy?

The RATE study did not enroll CLL patients or follicular NHL patients who were receiving post-induction therapy. As such, there are no data in the RATE study that support using 90-minute RITUXAN infusion in these patients.^1,2

Are there safety risks with a faster infusion?

Yes. Please read the Warnings and Precautions section of the full prescribing information, as well as the BOXED WARNINGS. The rate of Grade 3 or 4 IRRs was 1.1% during the day of or day after the start of Cycle 2, and 2.8% cumulatively in Cycles 2-8. Adverse events reported in patients who received a 90-minute infusion on Cycle 2 Day 1 were typical of patients treated with R-CHEMO.^1-3

Did IRRs occur beyond Cycle 2?

Yes. However, for patients who received the faster infusion of RITUXAN on Cycle 2 Day 1, the incidence of IRRs typically decreased with subsequent infusions with the 90-minute administration. The total incidence of Grade 3 or 4 IRRs over Cycles 2 through 8 was 2.8%.^1-3

What were the most common Grade 3 or 4 AEs reported in the study?

Over the course of the study (Cycles 1-8), the most common Grade 3 or 4 AEs were neutropenia (18.7% Cycle 1, 22.0% Cycles 2-8), febrile neutropenia (3.9% Cycle 1, 6.3% Cycles 2-8), infection and infestations (1.9% Cycle 1, 5.8% Cycles 2-8), and leukopenia (4.1% Cycle 1, 4.1% Cycles 2-8).^1-3

Did any patients discontinue because of AEs seen with the 90-minute infusion?

Yes. A total of 2.7% of patients discontinued due to AEs. The most common AEs leading to discontinuation on or after Cycle 2 Day 1 were infection or infestations and cardiac disorders. Discontinuation rates seen with the faster infusion were primarily due to non-drug–related issues. A total of 83.5% of patients (303/363) received at least 6 cycles of RITUXAN therapy. Of the 68 patients who discontinued on or after Cycle 2, 12 were due to AEs. The other 56 patients discontinued due to physician decision (13), patient decision (6), death (6), disease progression (3), lost to follow-up (3), or other reasons (25).^1,2

DLBCL=diffuse large B-cell lymphoma; NHL=non-Hodgkin's lymphoma; IRR=infusion-related reaction; CLL=chronic lymphocytic leukemia; R=RITUXAN; AE=adverse event.