Dr. Januario Castro from UCSD is looking to combine three potent non-chemo drugs to fight one of the most aggressive turns that chronic lymphocytic leukemia (CLL) can take, namely when it transforms into a diffuse, fast-moving large B cell lymphoma called Richter’s Syndrome (RS) or Richter’s Transformation (RT).
Methylprednisolone is a steroid and is one of the oldest therapies used to treat many cancers.
Lenalidomide is an immune modulating drug that has proven powerful activity in many blood cancers, including CLL (although for CLL only within a clinical trial setting).
Obinutuzumab is a 3rd generation monoclonal antibody that packs a strong punch in CLL.
By massively magnifying the dose with high-dose methylprednisolone or HDMP and adding in the latest anti-CD20 antibody, obinutuzumab (Gazyva) and lenalidomide (Revlimid), Dr. Castro believes we can get strong results without using chemotherapy against this killer lymphoma.
Take Away Points:
- As therapies get better for many with CLL, more patients are escaping control by presenting with Richter’s Transformation (RT), a very aggressive form of lymphoma.
- Minimum survival for RT in the past was 6 months.
- Be suspicious and insist on a biopsy if the pace of the cancer’s growth accelerates, or if new systemic symptoms develop, such as fevers or weight loss begin.
Richter’s transformation can present even when there has been no prior treatment of CLL, but is probably more common when the DNA has been damaged by prior chemotherapy.
It is not likely that the new oral therapies actually increase the risk of RT.
They do a good job of controlling the CLL, but are much less reliably effective in knocking down RT. Therefore, it is often Richter’s Transformation that is the path to escaping control of the new drugs and is the diagnosis when the disease becoming active again.
Traditionally RT was thought to develop in only 5-10% of CLL patients, but the number may be growing as we are living longer and receiving more treatments. For most, and there are frequent exceptions, the only viable long-term strategy is a high-risk allogeneic stem cell transplant. However, many patients cannot tolerate the chemo punch needed to knock down the RT in order to give the transplant a fighting chance, let alone struggle through the rigors of the transplant itself.
Dr. Castro is trying to develop a better option.
CLL is a rare cancer and Richter’s Transformation is an even rarer complication, so clinical trials and the progress they might offer are slow to accrue.
Listen to our discussion about the abstract from the 2015 iwCLL meeting when we sat down at the American Society of Hematology Annual meeting held in Orlando, FL in December 2015.
You can read the abstract about this combination therapy here. We will update this article when the trial opens and is accepting new patients.
Brian Koffman, MD 2/8/16