Rituxan and Treanda for CLL

Rituximab has been shown to prolong survival when used with chemotherapy in CLL.
The findings come from a comparative analysis of two completed national phase II and phase III clinical trials. There is insufficient evidence at this time to support or refute the use of single-agent rituximab or a rituximab-containing chemotherapy regimen in patients with chronic lymphocytic leukemia (CLL). Rituxan is not listed by NCCN for CLL as a single agent, except in the elderly.

Treanda is now FDA approved. A study of with Treanda (bendamustine)published in the Journal of Clinical Oncology in May 2005 showed significant activity of Treanda and Rituxan® (Rituximab) for the treatment of relapsed or refractory low-grade NHL or mantle cell lymphoma. A multicenter U.S. and Canadian trial of Treanda evaluated Treanda in combination with Rituxan in 67 patients with indolent or mantle cell lymphoma who had failed chemotherapy was presented at ASH 2005. Thirty-seven per cent had also failed Rituxan. The overall response rate was 87% with complete responses observed in 33%. The most frequent complications were related to reversible myelotoxicity.

On October 31, 2008, the U.S. Food and Drug Administration (FDA) approved bendamustine hydrochloride (TREANDA®, Cephalon, Inc.), an intravenously administered alkylating agent, for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

Putting the two drugs together is still in studies but the regimen already has guideline support. In a Phase II clinical trial, the combination of Treanda® (bendamustine) and Rituxan® (rituximab) produced promising results among patients with relapsed chronic lymphocytic leukemia (CLL). These results were presented at the 50th Annual Meeting of the American Society of Hematology.These results have led to a new trial comparing the efficacy of Treanda and Rituxan to Fludara® (fludarabine), Cytoxan® (cyclophosphamide) and Rituxan for treatment of newly diagnosed patients, NCT00769522. This randomized phase III trial is studying fludarabine, cyclophosphamide, and rituximab to see how well they work compared with bendamustine and rituximab in treating patients with previously untreated B-cell chronic lymphocytic leukemia. In this study, Treanda and Rituxan are the standard arm.

German researchers have also performed a randomized trial comparing BOP (bendamustine, oncovin and prednisone) to COP (cyclophosphamide, oncovin and prednisone) in a randomized trial of 513 patients with untreated indolent and mantle-cell lymphoma who were randomly assigned to bendamustine/rituximab (BR) or R-CHOP, and the initial results were presented at the 2009 American Society of Hematology annual meeting. All patients with FL (N = 279, median age 60) had defined indications for treatment. The overall response rate with BR was 93%, and the complete response rate and progression-free survival were superior to those seen with R-CHOP
The 2011 NCCN treatment guideline recommends the following:

•Treanda as a single agent as initial therapy for CLL
•Treanda as a single agent or in combination with Rituxan® (rituximab) for treatment of CLL that has recurred following prior therapy (second-line therapy.

•Treanda with or without Rituxan as first-line therapy for follicular lymphoma or mantle-cell lymphoma (p.FOLL-B) and this is a category 1 recommendation.

Kath R, Blumenstengel K, Fricke HJ, Höffken K (January 2001). "Bendamustine monotherapy in advanced and refractory chronic lymphocytic leukemia". J. Cancer Res. Clin. Oncol. 127 (1): 48–54

Robinson KS, Williams ME, Cohen P, et al. Bendamustine HCL (TREANDA) plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin’s lymphoma: a phase II study. Blood. 2005;106:271a, abstract # 923.

Friedberg JW, Cohen P, Cheson BD, et al. Bendamustine HCL (Treanda) results in high rate of objective response in patients with rituximab-refractory and alkylator-refractory indolent B-cell non-Hodgkin’s lymphoma (NHL): results from a phase II multicenter single-agent study (SDX-105-01). Blood . 2005;106:70a, abstract # 229.

Imrie K, Stevens A, Meyer R, Hematology Disease Site Group. Rituximab in lymphoma and chronic lymphocytic leukemia: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2005 Dec 22. 46 p. (Evidence-based series; no. 6-8). [65 references]

W. G. Wierda Current and Investigational Therapies for Patients with CLL
Hematology, January 1, 2006; 2006(1): 285 - 294.

Huhn D, von Schilling C, Wilhelm M, et al. Rituximab therapy of patients with B-cell chronic lymphocytic leukemia. Blood. 2001;98:1326–1331.

Fischer K, Stilgenbauer S, Schweighofer CD et al. Bendamustine in combination with rituximab (BR) for patients with relapsed chronic lymphocytic leukemia (CLL): a multicentre phase II trial of the German CLL Study Group (GCLLSG). Presented at the 50th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2008. Abstract 330.

Comments

[P. Livingston]

My husband has had CLL/ITP for ten years. It is just this past year that his numbers have fallen thru the floor. He has been in ER 4 times in 6 weeks with hgb of 4.1 to 5.3 which they can get up to 6.6 to 9.1 after 4-6 units of whole blood but it only lasts 4 days and his energy is completely gone. WBC 74-108 - platelets have always been low - can't count accurately usually around 5K. Oncologist is suggesting rituxan (which he has taken numerous times only this time along with treanda. Will this help our situation?

[cancer treatment]

The central question is: Is this from autoimmune hemolytic anemia, or from replacement of bone marrow by CLL cells. In either case Treanda can help, but if autoimmune, other treatments can also help. Please ask your oncologist.

My best wishes and encouragement.

[D. Richter]

My husband has had CLL for 14yrs and has had some hemolytic enemia but with rituxan every 3 months and IGG every 3 months we have been very lucky. The last 2 times he received rituxan he got the chills. He has also now wasting and has lost weight. We found he now might have renal cell carcinoma kidney and lung.He just had treatment for cll with rituxan and treanda split into 2 days and on the 3rd day nulasta.After blood work his white count went up why?

[cancer treatment]

This can happen when the treatment clears space within the bone marrow in which new cell production can now take place. These are normal cells and it may be a sign of response. Of course, it needs to be evaluated as there are also other potential reasons.

[D. Richter]

And what would the other potential reasons be?

[PML / Rituxan]

To all of you out there using Rituxan please be aware of the many life threatening side effects. My mother was treated for many years with Rituxan, her last was a Benamustine/Rituxan combo for NHL under a new Onocologist. She managed to survive almost 30yr's most of it with one kidney that she had removed from cancer. After the last treatments her ANC's and health dramatically dropped and she ended up with PML from the JC Virus and a weakened immune system. She died a terrible death in 2 short months after the PML diagnosis. Rituxan is very hard on PT's over 70 with weakened immune systems (warnings state this), they need to be very closely monitored. Always be an advocate for yourself and research, research, research. Unfortuanetly doctor's don't know everything!