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October 2022 CLL Bloodline

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

Over the course of a year of monthly meetings, The CLL Bloodline will teach the BASICS needed to understand CLL, bring news, help with the acronym and new vocabulary, and offer simple, fun quizzes.

MONTHLY QUIZ: The spleen is important in CLL. All the following are true EXCEPT:

  1. The white pulp of the spleen acts as an immune organ, much like a giant lymph node.
  2. The red pulp acts to rid the body of old red blood cells and platelets and recycles their contents.
  3. The spleen can serve as a backup to the bone marrow by releasing blood cells into circulation.
  4. One can live without a well-functioning spleen or even after its total removal.
  5. 30% of people have a tiny 2nd spleen called a splenule or accessory spleen that grows if the spleen is removed.
  6. Removal of the spleen is sometimes done prophylactically in CLL to lower the risk of infections.

The correct answer is #6. The spleen helps the body remove certain common “encapsulated” bacteria that can cause pneumonia, meningitis, and other infections, and its removal is associated with more serious infections.

NEWS: We are excited to announce the inaugural recipient of CLL Society’s 2022 Young Investigator Award, Dr. Christine Ryan. Her research is titled “BH3 Profiling to Identify Novel Vulnerabilities in Richter’s Syndrome (RS).” She hopes that by understanding which proteins the RS cells depend on, someday, targeted therapies might be developed to block those pro-survival proteins so that RS can be treated more effectively. This happened a decade ago in CLL/SLL with the breakthroughs in understanding the biology that led to all the new target therapies.

ODAC (Oncology Drug Advisory Committee) of the FDA sadly voted 8 to 4 no to the question: Is the benefit-risk profile of duvelisib favorable in patients with relapsed or refractory CLL or SLL after two prior therapies? This vote does not mean duvelisib will be pulled, but its future is in doubt. CLL Society spoke in favor of keeping duvelisib. We are now working with the FDA to see if there is a way to both have protection from serious side effects, and duvelisib available.

We are grateful to all those who have supported us, enabling our growing research and advocacy efforts. Thank you.

THE BASICS: In an earlier Bloodline, we discussed factors that decide your choice of therapy. This month we explain targeted therapies that are generally our best choice. This gets detailed, but the crucial point is that “targeting” drugs work.

Targeted Therapies (TT) are drugs that interfere with specific “targets” critical to cancer cell growth and survival. In CLL, these include monoclonal antibodies (mAbs) that attack a specific protein found on the cells’ surface. This protein may be found on some normal cells but not most cells. Examples include rituximab, ofatumumab (now rarely used), and obinutuzumab, that target CD20 found only on CLL and normal B cells. Another TT are TKIs or tyrosine kinase inhibitors that inhibit enzymes such as BTK, which is blocked by ibrutinib, acalabrutinib, and pirtobrutinib aka LOXO-305 (experimental) or PI3K blocked by idelalisib and duvelisib (at least for now). Both BTK and PI3K are part of the B cell receptor (BCR) pathway that cancer has become “addicted” to and is critical to its survival. Blocking it turns off the messages the cancer gets to live long and proliferate. Venetoclax and the experimental lisaftoclax are not TKIs. They turn back on apoptosis or programmed cell death, leading to the rapid killing of the CLL cells. Those CLL cells had turned off that death pathway to improve survival. Unlike chemotherapies, TT does not damage DNA or target all fast-growing tissues, cancerous or not. The important point is that because TTs are “targeted,” they tend to cause less collateral damage. They are often newer, more effective, and expensive than “chemo” discussed in the last Bloodline.


Immunotherapy therapy uses our immune system to fight cancer and is made from living organisms. They include mAbs (monoclonal antibodies) and CAR-Ts (genetically modified T cells). It may also be called biological therapy or targeted therapy.