ASH 2011: Major Advances in Allogeneic Stem Cell Transplant Offer New Hope For Patients with Hematologic Malignancies

By Koen van Besien, MD, PhD

Allogeneic transplant can be curative for patients with lymphoma and is often effective in difficult situations where other treatments have failed. Unfortunately very few of us have suitable sibling donors and in a multi-ethnic society such as the US, finding HLA-identical donors in the transplant registry can also represent a challenge.  Several studies presented at the Annual Society of Hematology meeting offer evidence of rapid progress and increased success in the field of mismatched transplantation.  Dr. Symons from John’s Hopkins used mismatched related donors  ( also called haplo-identical donors i.e relatives who are partially HLA-identical) and with a novel chemotherapy regimen and  GVHD prophylaxis reported a low risk for graft vs host disease and excellent outcomes in patients with very high risk disease. Using similar technology even better results were reported by Dr. Bashey from Atlanta. He reported that the outcomes of such haplo-transplant were similar to those of transplants from HLA-identical siblings.  We used a slightly different approach and combined a haplo-identical transplant with an umbilical cord blood graft. In this procedure, the umbilical cord blood graft tends to assure long term hematopoiesis and may provide a more robust immune system with very little chronic graft vs host disease. We presented data on 51 patients with hematologic malignancies and the group from NIH used a similar approach to treat 10 pts with aplastic anemia. Both groups showed excellent rates of recovery and a high percentage of patients achieving prolonged remissions.  Dr. van Rood showed that the choice of umbilical cord graft may minimize the risk for disease recurrence.  It is too early to know which of these approaches, haplo or haplo-cord transplantation will ultimately become widely accepted, but the field is moving rapidly and options for patients who lack a sibling donor are rapidly improving.

Allogeneic transplantation for Hodgkin’s lymphoma

Though most patients with Hodgkin’s Lymphoma (HL) are cured with their initial treatment, a small percentage of them fail to achieve remission or relapse after initial treatment. Such patients usually receive a salvage chemotherapy regimen followed by autologous stem cell transplantation. However, only half of those undergoing autologous transplant are cured, and that percentage is even lower for those with incomplete responses to salvage. Using an innovative approach, Continue reading “ASH 2011: Major Advances in Allogeneic Stem Cell Transplant Offer New Hope For Patients with Hematologic Malignancies”

Update from ASH 2011: New treatments for mantle cell lymphoma are on the horizon

By Peter Martin, MD

Update: this study is closed to enrollment. 

Arguably the most exciting news to come from the American Society of Hematology (ASH) meeting this year was the presentation by Dr. Michael Wang of preliminary results from the phase 2 trial of PCI-32765 for patients with previously treated mantle cell lymphoma (MCL). PCI-32765 is an oral (pill form) inhibitor of an enzyme called Bruton’s Tyrosine Kinase (BTK). BTK plays an important role in communicating pro-survival signals from the cell microenvironment to the nucleus of the cell. Inhibition of BTK by PCI-32765 demonstrated promise in patients with MCL in a national phase 1 that was open at Weill Cornell Medical College. This phase 2 study, also open at Weill Cornell, demonstrated a response rate of approximately 60-70% with little toxicity (mostly mild gastrointestinal side-effects). It is too early to determine how long these effects will last or whether there are any side effects that will become apparent with longer treatment. Click here for more information about this trial.

Dr. Beata Holkova presented the results of a National Cancer Institute (NCI) phase 2 study that was open at several institutions across the country, including Weill Cornell. The trial evaluated the combination of bortezomib (FDA-approved for treatment of patients with previously treated MCL) plus the histone deacetylase inhibitor vorinostat. The combination demonstrated synergistic activity in preclinical studies and showed promised in earlier trials in patients with multiple myeloma. Preliminary results from this NCI trial were encouraging, particularly in the group of patients with MCL that had never been treated with bortezomib. The trial is ongoing. Click here for more information about this study.

Update from ASH 2011: Rituximab improves survival in patients with mantle cell lymphoma

By Peter Martin, MD

Until recently, the role of rituximab in treatment of mantle cell lymphoma (MCL) was unclear. Prior randomized trials demonstrated improved response rates to chemotherapy when combined with rituximab, but unlike other lymphomas, it had failed to demonstrate an improvement in survival. Two abstracts presented at the recent American Society of Hematology (ASH) meeting provided encouraging evidence regarding this most-important outcome.

Dr. Simon Rule presented the results of the recent UK National Cancer Research Institute trial comparing fludarabine/cyclophosphamide (FC) to FC plus rituximab (FCR) in patients of all ages with newly diagnosed MCL. The trial enrolled 370 patients with mostly intermediate and high-risk MCL and followed them for an average of 39 months. The addition of rituximab to FC improved response rate, complete response rate, time to progression, and overall survival. Combined with recent evidence from data registry studies and the data that has accumulated from prior trials, it is clear that standard of care first-line treatment of MCL should include rituximab.

Updated results from a European Mantle Cell Lymphoma Network trial (also presented at the meeting in Lugano last summer and discussed by Dr. Rebecca Elstrom in this blog) confirmed that rituximab maintenance administered to patients over 60 years of age after R-CHOP chemotherapy provided a significant survival benefit. Although longer follow-up and confirmatory trials are needed, rituximab maintenance may be considered standard of care for older patients not receiving more aggressive induction/consolidation regimens. The upcoming Intergroup trial for patients over 60 years of age will feature randomization between rituximab maintenance and maintenance with lenalidomide plus rituximab.