Table VI.
Consensus panel dose recommendations and dose reductions with bendamustine therapy.
| Dose recommendation | Dose (days 1 and 2) | Cycles | Notes |
|---|---|---|---|
| CLL | |||
| Front line, single agent | 100 mg/m2 every 4 weeks | 6 | Rarely used in this situation |
| Front line + rituximab | 90 mg/m2 every 4 weeks | 6 | |
| R/R ± rituximab | 70 mg/m2 every 4 weeks | 4 | |
| iNHL | |||
| Front line + rituximab | 90 mg/m2 every 4 weeks | 6 | No rituximab maintenance |
| R/R ± rituximab | 70–90 mg/m2 every 4 weeks | 4 | |
| Follicular | 6 | ||
| Waldenstroem | 4–6 | ||
| Marginal zone | 4–6 | ||
| Aggressive non-Hodgkin lymphoma | |||
| Front line + rituximab | 120 mg/m2 every 3 weeks | 6 | Reduced as needed |
| R/R ± rituximab | 90–120 mg/m2 every 3–4 weeks | 6 | Clinical experience suggests that 120 mg/m2 is not well tolerated by a significant sub-population of patients |
| Peripheral T-cell lymphoma (includes angioimmunoblastic and NOS) | |||
| R/R | 90–120 mg/m2 every 3 weeks | 4–6 | Start with 120 mg/m2; can be reduced to 90 mg/m2 if needed |
| Mantle-cell lymphoma | |||
| Front line + rituximab | 90 mg/m2 every 4 weeks | 6 | Patients not considered for high-dose therapy |
| R/R ± rituximab | 90 mg/m2 every 4 weeks | 4–6 | Can be reduced to 70 mg/m2 if needed. |
| Hodgkin lymphoma | |||
| R/R | 90 mg/m2 every 3 weeks | 4–6 | No difference has been observed at doses 100–120 mg/m2Number of cycles based on tolerance |
| Multiple myeloma | |||
| Front line single agent | 100 mg/m2 every 4 weeks | 6 | Label suggests 120–150 mg/m2, but this is not recommended by the panel |
| Front line combination therapy | 60–90 mg/m2 every 4 weeks | 6 | Start at 60 mg/m2 and escalate to 90 mg/m2 with tolerability |
| R/R | 60–90 mg/m2 every 4 weeks | 6 | |
| Dose reduction | |||
| CLL | |||
| Front line + rituximab | 90 to 70 mg/m2 | ||
| R/R + rituximab | 70 mg/m2 to dose delay* | ||
| iNHL | |||
| Front line or retreatment | 60-min infusion of 500 mL | To reduce skin reactions The reconstituted concentrate (50 mL) should be diluted immediately with 0.9% sodium chloride solution, otherwise there is an increased risk of rash Once reconstituted and diluted it is stable for 3–4 h at room temperature or for 48 h in the fridge | |
| Dose reduction | 90 to 70 mg/m2 | Discontinue if still problems at 70 mg/m2 | |
| Aggressive non-Hodgkin lymphoma | |||
| Front line | 120 to 90 mg/m2 | ||
| R/R | 1st reduction: 120 to 90 or 90 to 70 mg/m22nd reduction: 90 to 70 mg/m2 | In a Japanese/Korean phase II study, the 2nd dose reduction was from 90 mg/m2 to 60 mg/m2 | |
| Hodgkin lymphoma | |||
| R/R | 90 to 70 mg/m2 | ||
| Multiple myeloma | |||
| Monotherapy | 100 to 70 mg/m2 | ||
| Combination therapy | 90 to 60 mg/m2 |
iNHL: in the front-line setting, bendamustine should not be used as a single agent. Consider pre-medicating with dexamethasone (8 mg, IV, in combination with 5-HT3 antagonist) or hydrocortisone (50–100 mg). Normally recommend dose delay before dose reduction. Use dose reduction as a first step in those patients with transient non-hematological toxicity.
Aggressive non-Hodgkin lymphoma: BR can be used in those patients who cannot use R-CHOP or a CHOP-like regimen. Definition includes follicular lymphoma, grade 3b. No recommendations for Burkitt’s lymphoma or lymphoblastic lymphoma.
T-cell lymphoma: bendamustine has no known role in the front-line setting.
Mantle-cell lymphoma: further dose reductions of bendamustine are needed when in combination with potentially myelosuppressive agents (e.g. ibrutinib, bortezomib, lenalidomide).
Multiple myeloma: bendamustine should be dosed on two days (Days 1 + 2, Days 1 + 8 or Days 1 + 4) within a 28 day cycle. Bendamustine would be considered first-line therapy in non-transplant-eligible patients.
*Doses < 60 mg/m2 are considered sub-therapeutic and dose delays are preferred.