Novel induction regimens in transplantation for mantle cell lymphoma – pro

Lay Summary: Stem cell transplantation is standard of care for mantle cell lymphoma.

Mantle cell lymphoma is a fairly recently identified subtype of non-Hodgkin’s lymphoma. Regarded as a low-grade tumour in previous classifications, it has a median survival of only 36 months and is incurable by current treatment approaches. Widespread disease is usually present at diagnosis involving lymph nodes, spleen, bone marrow and extranodal sites such as the gastrointestinal tract. Initial response rates to treatment are high but the majority of patients relapse within 2 years. There is some evidence that high dose myeloablative chemotherapy and total body irradiation followed by stem cell rescue in first remission may give long-term disease-free survival. Both rituximab and Velcade are being clinically investigated as a part of induction. A recent study that used Rituxan reported good results in comparison with historical controls. 24 patients with newly diagnosed mantle cell lymphoma were treated with four to six courses of DHAP-rituximab followed by autologous stem cell transplantation for patients <65 years. Three-year overall survival (OS) and event free survival (EFS) rates were 69% and 65% respectively, for the 24 patients. In intent-to-treat analysis, 3-year OS and EFS were 75% and 76% for the 17 patients < 65 years old.
This is true even for partial resonses after initial chemotehrapy. A study by the European Mantle Cell Lymphoma Network established autologous stem cell transplant as the standard of care. Patients receiving upfront CHOP or CHOP-like induction, followed by autologous stem cell transplant, had prolonged progression-free survival, compared with those on interferon maintenance (P = .0108).1 The study also showed that patients who achieved complete remission, vs partial remission, had the greatest benefit, although there was a suggestion of benefit even with partial remission. The study was not designed to evaluate overall survival, but a strong trend favored the transplant arm.

A phase II study investigating Velcade in a transplant setting but after induction is ongoing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with an autologous stem cell transplant may allow more chemotherapy to be given so that more cancer cells are killed. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib after combination chemotherapy, monoclonal antibody therapy, and an autologous stem cell transplant may kill any remaining cancer cells or keep the cancer from coming back.

The 2011 NCCN also recommends autologous transplantation after Hyper-CVAD but it does not recommend it after a complete response and after a partial response it recommends on p. MANT-@ a clinical trial, including of autologous or allogeneic transplantation. Curiously on the next page is appears to recommend autologosu or allogeneic transplantation and does not mention a clinical trial. This is corroborated on P. MS-82. I read this as a recommendation for an autologous or allogeneic transplant as consolidation for any responsive mantle cell lymphoma., 2017

Dreyling M, Lenz G, Hoster E, et al: Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: Results of a prospective randomized trial of the European MCL Network. Blood 105:2677-2684, 2005.

2. Hermine O, Hoster E, Walewski J, et al: Alternating courses of 3x CHOP and 3x DHAP plus rituximab followed by a high dose ARA-C containing myeloablative regimen and autologous stem cell transplantation increases overall survival when compared to 6 courses of CHOP plus rituximab followed by myeloablative radiochemotherapy and ASCT in mantle cell lymphoma: Final analysis of the MCL Younger Trial of the European Mantle Cell Lymphoma Network. 2012 ASH Annual Meeting. Abstract 151.

3. Graf SA, Stevenson PA, Holmberg LA, et al: Rituximab maintenance therapy after autologous stem cell transplantation improves survival of patients with mantle cell lymphoma. 2014 ASH Annual Meeting. Abstract 3985. Presented December 8, 2014.

Imrie K, Rumble RB, Crump M, Advisory Panel on Bone Marrow and Stem Cell Transplantation, Hematology Disease Site Group. Stem cell transplantation in adults: recommendations. Toronto (ON): Cancer Care Ontario Program in Evidence-based Care; 2009 Jan 30. 78 p. (Recommendation report; no. 1). [66 references]

Kiss TL, Mollee P, Lazarus HM, Lipton JH. Stem cell transplantation for mantle cell lymphoma: if, when and how? Bone Marrow Transplantation. 2005;36:655–661

DE GUIBERT S , Jaccard A, Bernard M, Turlure P, et alRituximab and DHAP followed by intensive therapy with autologous stem-cell transplantation as first-line therapy for mantle cell lymphoma.Haematologica. 2006;91:425-6.

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