Large Granular Lymphocytic Leukemia: What We CLL Patients Can Learn from a Novel Therapy for a T Cell Cancer

This week in Blood there was a very interesting article published on a very rare form of blood cancer, LGLL or large granular lymphocytic leukemia.

The abstract stated:

T-cell large granular lymphocyte leukemia (LGLL) is a rare clonal disease often associated with rheumatoid arthritis (RA) and manifests chiefly as neutropenia and recurrent infections. Immunosuppressive agents are the mainstay of treatment, but long-term remissions are rare. We report 2 cases of LGLL in patients with RA successfully treated with rituximab, a monoclonal antibody specific of B cells and approved for treating RA. The first patient experienced a complete LGLL remission that was sustained during the 8-year follow-up after the first rituximab infusion. In the second patient, rituximab therapy was followed by immediate neutropenia recovery and then by marked shrinkage of the LGLL clone 1 year later. The paradoxical efficacy of this specific anti–B-cell drug on a monoclonal T-cell disease suggests that some cases of LGLL may be reactive manifestations of chronic autoantigen stimulation rather than true malignancies.

I added the bold because this jamming on of reactive pathways with all its nasty downstream consequences is similar to what we are trying to block with BTK and PI3K inhibitors in CLL. In CLL, we are trying to shut down the constitutively stimulated B cells by blocking their pro-survival communication, proliferative, and homing instincts.

Further down is the report we find:

As illustrated by our first patient, T-cell LGLL is frequently associated with concomitant low-grade B-cell dyscrasias, such as monoclonal gammopathy of unknown significance or chronic lymphocytic leukemia, suggesting that a common antigen may drive both T- and B-cell proliferation.

That is powerful talk. Yet to be proven, but worthy of more research.

Maybe that is why anti-T cells therapies such as ciclosporin help some in CLL, yours truly included. 

Everything in the complex immune system is so connected.

The whole Blood article is short and I recommend it.

This type of creative systemic thinking is exactly what will be needed to completely and finally shut done the monoclonal B cell factory that is CLL. We may need to read the green tea leaves in more than our CLL teacups to find our answers. We need to look at the research being done in other liquid and solid cancers. Some of the fantastic new immune therapies in metastatic melanoma as detailed in my prior post from ASCO 2013 immediately come to mind as future paths to pursue. 

Last, but not least, and while the issue may be just semantic and this is only two cases, all of us with  CLL would much prefer to live with a "reactive manifestations of chronic autoantigen stimulation rather than true malignancies", especially if such labeling leads to better therapeutic approaches and better outcomes.

I am off to Germany on Monday for iwCLL. Send me your burning thoughts and questions that I might share with all the CLL gurus gathered in Cologne.

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Immunotherapy for Metastatic Melanoma

The big news out of ASCO 2013 was not about CLL, but about metastatic melanoma.

ASCO is well known to be more of a solid tumor meeting and it lived up to its reputation.

The big buzz is that now oncologists are using a new class of immune therapies that takes the brakes off the immune system so that it can aggressively attack the cancer.

Harnessing the immune system has long been an elusive goal in cancer therapy.

Until recently the best durable response rate in advanced melanoma was about 5% with a very difficult interleukin 2 protocol that made patients feel just awful.

Now it is over 70% and quite durable with simple combination of two separate immune therapy. And with a manageable side effect profile.

Moreover, the breakthrough PD- L1 antibody drugs discussed may have potential in a broad range of cancers, including blood cancers. It is important that those of us with CLL follow the developments in other tumor therapy so that we can be aware of any possible application or parallel research for our particular malignancy.

Exciting and hopeful times for those of us with cancer.

I am grateful to Andrew Schorr and the dedicated professional team at Patient Power for providing the support to do these fun interviews with these pioneering doctors. Please check out Patient Power over the next few weeks for more interviews from ASCO 2013.

Here's a link to Patient Power for the the first part of this same interview on the tremendous parallel progress in targeted therapy for advanced melanoma with a specific mutation that until recently had been well known as a fast working assassin for most victims.

Targeted therapy.

Immunotherapy.

Logical and complementary drug combinations.

This is the future not just for the treatment of melanoma, but for all of oncology.

Soon I will be posting my interviews with several CLL experts done in partnership with Patient Power.

Dr. Lynn Mara Schuchter on the Latest News on Immunotherapy for Advanced Melanoma from ASCO 2013