Noncovalent BTK Inhibitors May Fill Unmet Needs in CLL and Other Top ASH Takeaways


Laura J. Zitella, MS, RN, ACNP-BC, AOCN, highlights her top takeaways from the 64th American Society of Hematology Annual Meeting and Exposition.

Laura J. Zitella, MS, RN, ACNP-BC, AOCN

Laura J. Zitella, MS, RN, ACNP-BC, AOCN

Data presented at the 64th American Society of Hematology Annual (ASH) Meeting and Exposition demonstrated successful efforts in improving quality of care and reducing symptom burden for patients, according to Laura J. Zitella, MS, RN, ACNP-BC, AOCN.

Specifically, data which supports liberalizing diets for patients undergoing transplant may improve patient experiences during treatment.1 In addition, various trials at the meeting showcased promising data with BTK inhibitors. These oral treatments are generally well tolerated, signaling that they may be able to fill unmet needs for patients with adherence or other hurdles with accessing alternative treatments.

Zitella, who is a nurse practitioner in the Department of Hematology, Blood & Marrow Transplant, and Cellular Therapies Program at the UCSF Helen Diller Family Comprehensive Cancer Center and an associate clinical professor with the School of Nursing University of California, San Francisco, recently spoke with Oncology Nursing News® to discuss which data from the 2022 ASH meeting might have the greatest impact on nurses working in hematologic oncology.

Oncology Nursing News®: Could you contextualize the neutropenic diet and expand on the data supporting no longer using it and what that may mean for patients undergoing transplant?

Zitella: Just to give a little bit of background, there’s never been any evidence that supports the use of the neutropenic diet. It started in the 1970s, when researchers observed that fresh fruits and vegetables were contaminated with E. coli and Pseudomonas and other gram-negative bacteria. At that time, they felt it was prudent to restrict fresh fruits and vegetables from patients’ diet in an effort to decrease infection, but there’s never been a study that showed that it decreased the risk of infection.

As far back as 20 years ago, there have been individuals questioning this because nutrition is such an important issue for our patients and restricting their diets is a burden. [However, these] initial studies were all very small, retrospective, and people really clung to the idea of the neutropenic diet.

I think the first important study that was done was at [the University of Texas] MD Anderson [Cancer Center] by a nurse researcher Alison E. Gardner, [RN, AOCNS, PhD], who looked at patients with acute myeloid leukemia undergoing induction therapy, and showed at that time that there was no role for a neutropenic diet.1 And so some institutions [moved away from the diet]. One of those institutions was Northwestern Memorial Hospital, [which] abandoned the neutropenic diet. [Investigators] did a retrospective study [with] their transplant patients that showed that there was no increased risk of infection [with] a more liberal diet.2

The study that came out at ASH, in a transplant population—which is the most immunocompromised population—really highlights the issue. Hopefully, this will be enough to convince [individuals] to abandon the neutropenic diet and liberalize it because safety has been demonstrated.3

The other important takeaway for nurses is what you tell patients if you’re not going to recommend a neutropenic diet. The government has a very nice website called [where] there are some really simple [safety concepts, such as] clean your hands and surfaces and wash fresh fruits and vegetables carefully, separate raw meats and eggs from other foods. keep the refrigerator at the right temperature, don’t leave anything out of the refrigerator for more than 2 hours that’s perishable, and make sure that you cook foods to the appropriate temperature.

How do you interpret the data surrounding BTK Inhibitors? Do they hold potential to change practice?

There were a couple abstracts on BTK inhibitors that I thought were really interesting. Starting with chronic lymphocytic leukemia [CLL], we have 3 options for BTK inhibitors: ibrutinib [Imbruvica], which was the original BTK inhibitor, and then we have second generation BTK inhibitors, zanubrutinib [Brukinsa] and acalabrutinib [Calquence].

The ALPINE study [NCT03734016] compared 2 BTK inhibitors head-to-head.4 It was a comparison between zanubrutinib and ibrutinib for relapsed or refractory chronic lymphocytic leukemia [CLL]. It was presented at ASH this year and showed that zanubrutinib had a better overall response rate and progression-free survivalthan ibrutinib. This is pretty important to be able to compare 2 very good treatments for CLL head-to-head, especially because there are some significant adverse effects associated with BTK inhibitors, [such as] atrial fibrillation, and zanubrutinib has a lower rate of atrial fibrillation than ibrutinib. These are very important data, especially for taking care of patients with CLL and trying to decide what [treatment] is the optimal.

There was [also] an abstract presented looking at a BTK inhibitor called pirtobrutinib.5 These are early data, but what was interesting about pirtobrutinib is that it is a noncovalent BTK inhibitor and the other BTK inhibitors that we have currently are covalent. So, if a patient has CLL that progresses on a BTK inhibitor, using an alternate BTK inhibitor isn’t effective. However, pirtobrutinib works differently. What was interesting about this abstract is that it showed that it had some effectiveness in patients who had prior covalent BTK inhibitor use. That is going to fill an unmet need in patients with CLL who progressed on the current BTK inhibitors that we have.

There are other treatment options for CLL but being on an oral medication is an attractive option for patients. Some other options are rituximab [Rituxan] and venetoclax [Venclexta], obinutuzumab [Gazyva], and chemotherapy, although chemotherapy is generally not used in the setting of CLL. But there are a lot of advantages to having a single-agent oral medication that can be used for patients with CLL.

The other BTK inhibitor data that were interesting were in mantle cell lymphoma, [in which] there is not a clear standard of care. There’s a lot of different approaches to first-line therapy. But one standard approach for younger patients who can tolerate intensive therapy is induction chemotherapy followed by autologous transplantation.

[One particular] abstract looked at adding ibrutinib, a BTK inhibitor, to standard induction therapy, followed by autologous transplant and then using ibrutinib in the maintenance setting.6 Investigators showed that adding ibrutinib was more effective than not adding ibrutinib. This is very interesting, because I think that’s going to lead to the next question, which is: Do we need to continue to recommend autologous transplant or would the addition of a targeted agent, such as ibrutinib, be just as effective?


  1. Gardner A, Mattiuzzi G, Faderl S, et al. Randomized comparison of cooked and noncooked diets in patients undergoing remission induction therapy for acute myeloid leukemia. J Clin Oncol. 2008;26(35):5684-5688. doi:10.1200/JCO.2008.16.4681
  2. Trifilio S, Helenowski I, Giel M, et al. Questioning the role of a neutropenic diet following hematopoetic stem cell transplantation. Biol Blood Marrow Transplant. 2012;18(9):1385-1390. doi:10.1016/j.bbmt.2012.02.015
  3. Stella F, Marasco V, Levati GV, et al. Non-restrictive diet does not increase infections in patients with neutropenia after stem cell transplantation: final analysis of the Neutrodiet multicenter, randomized trial. Presented at ASH 2022. December 10-13, 2022. Abstract 169.
  4. Brown JR, Eichhorst B, Hillmen P, et al. Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. Published online December 13, 2022. doi:10.1056/NEJMoa2211582
  5. Mato AR, Woyach, JA, Brown, JR, et al. Efficacy of Pirtobrutinib in Covalent BTK-Inhibitor Pre-Treated Relapsed / Refractory CLL/SLL: Additional Patients and Extended Follow-up from the Phase 1/2 BRUIN Study. Presented at ASH 2022. December 10-13, 2022. Abstract 961.
  6. Dreyling M, Doorduijn, JK,Gine E, et al. Efficacy and Safety of Ibrutinib Combined with Standard First-Line Treatment or As Substitute for Autologous Stem Cell Transplantation in Younger Patients with Mantle Cell Lymphoma: Results from the Randomized Triangle Trial By the European MCL Network. Presented at ASH 2022. December 10-13, 2022. Abstract 1.
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