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Chronic Lymphocytic Leukemia (CLL)

Overview

Supportive Care and AE

Treatment Considerations

Clinical Resources

Treatment considerations for TN and R/R CLL, including high-risk CLL

Among CLL patients^1,2

Graph of patients on active treatment and those in “watch and wait” category — Graph showing an approximate proportion of patients with CLL who need treatment right away (≈1/3), those who will not need treatment right away but will need it at some point (≈1/3), and patients with CLL that may never need treatment (≈1/3). Overall, ≈2/3 of patients are placed in the “watch and wait” category.

When do patients with CLL need treatment?

iwCLL indications for treatment^3,a

Lymph nodes

Massive (ie, ≥10 cm), progressive, or symptomatic

Liver and/or spleen size Massive

(ie, ≥6 cm below the left costal margin), progressive, or symptomatic

Constitutional symptom

Disease-related symptoms^b

Circulating lymphocyte count

Progressive ≥50% over a 2-month period, or lymphocyte doubling time <6 months^c

Platelet count

Worsening thrombocytopenia <100 x 10⁹/L due to progressive marrow failure^d

Hemoglobin

Worsening anemia <10 g/dL due to progressive marrow failure^d

Bone marrow

Progressive marrow failure as per above

Extranodal

Symptomatic or functional extranodal involvement (eg, skin, kidney, lung, spine)

^aAutoimmune complications (including autoimmune cytopenias) poorly responsive to corticosteroids or current treatment may represent an additional indication for change in treatment.

^bUnintentional weight loss ≥10% within the previous 6 months; significant fatigue (ECOG performance scale ≥2), fevers (38°C) for ≥2 weeks without evidence of infection; night sweats for ≥1 month without evidence of infection.

^cNon-CLL factors that may contribute to lymphocytosis (eg, infections and corticosteroids) should be excluded.

^dHemoglobin and platelet count cutoffs require consideration of the rate of decline. In certain patients, counts slightly below these levels may remain stable for an extended period and not require treatment initiation.

Decision making criteria in the treatment of B-cell malignancies^4-11

Criteria in the treatment of CLL — Selection of treatment in CLL depends on malignancy type, stage of disease, rate of disease progression, patient characteristics, evidence-based clinical practice guidelines, prognostic biomarkers, prior therapies, patient preference/access to care

Developing a treatment plan for patients with CLL involves shared decision-making between patients and providers after considering stage of disease, risk of progression, overall prognosis, and potential side effects^12,14
For patients with CLL in which treatment is indicated, the presence or absence of del(17p) and TP53 mutations are most often used to direct treatment selection¹³

Shared decision making between HCPs and patients

Leverage SHARE principles for shared decision making^14,16

Shared patient decision making occurs when HCP and patient work together to make a healthcare decision that is in the best interest of the patient

SHARE principles include “seek, help, assess, reach, and evaluate — To use share principles for shared decision making, seek your patient’s participation, help your patient explore and compare treatment options, assess your patient’s values and preferences, reach a decision with your patient, and lastly, evaluate your patient’s decision

To gain a medical oncologist’s perspective on how shared decision making impacts treatment selection in CLL, you will find Dr Thompson’s and Dr Roeker’s video and an infographic on CLL therapies in the related resources at the bottom of the page.

Related Resources

Downloadable PDFs

Shared Decision Making in Hematologic Malignancies

This slide deck aims to train HCPs to differentiate between clinical centric and shared decision making, and to understand the mutual benefits of shared decision making when treating hematologic malignancies.

Infographic: Leverage SHARE for shared decision making

This infographic summarizes opportunities to leverage SHARE principles for shared decision making.

CLL Therapy Overview and Clinical Considerations

Infographic for HCPs describing indications for treating CLL and current therapies.

Incorporating new treatments into the management of B-cell malignancies

This slide deck is intended to educate health care providers about strategies, solutions, and resources for incorporating new treatments into clinical practice for B-cell malignancies.

Potential Barriers and Solutions for Incorporation of New Treatments in B-Cell Malignancies

This infographic is intended to educate health care providers on potential barriers and solutions for incorporation of new treatments in B-cell malignancies.

(00:11) Lindsey Roeker:
So when I'm meeting a patient and talking to them about treatment options, I really consider two major factors. The first is comorbidities. So is this a patient who has a history of something that pushes me toward one treatment option, or another? Some things that I think about are cardiac comorbidities, renal dysfunction, history of bleeding. Those are the big ones that I'm thinking about that made me point me one direction or the other. I also talk about patient preferences, and that's a second huge piece of this because we have therapies that differ from one another in terms of duration, logistics of administration, and side effect profiles. So finding the right fit for the right patient is really important in this disease. We have therapies that can be given continuously. We have therapies that can be given as time-limited treatments, and really identifying what a patient's preference is, really helps in making that decision.

(01:08) Meghan Thompson:
So when I'm seeing a patient in the clinic and we're talking about treatment options, especially when we're talking about their initial treatment, I think it's really important to take the time to lay out a roadmap of what the options look like and then what are the side effects with each options. And then of course, any information we have from a CLL perspective and their other medical problems, what our recommendation really is.

(01:43) Meghan Thompson:
I do think that shared decision-making is super important in patients with CLL, especially when we're selecting an initial therapy and there might be multiple options present. Patients should be understanding of the side effects of treatment, the monitoring required with different treatment modalities, how long or how short patients are expected to be on therapy. So all of these things really come in, and I do find that sometimes if it's not an urgent indication, this can even take the course of multiple visits. But really empowering the patients, their caregivers, to be partners with you and really understanding what treatment will look like.

(02:28) Lindsey Roeker:
Couldn't agree more. I think having people go into their therapy, understanding what's expected makes everyone's job easier. It makes the patient's life easier because they're not faced with surprises and it makes the care team's job easier because they've set up expectations so that a patient knows what's coming. And I think those are really important pieces.

How do you approach shared decision making in CLL?

Dr. Lindsey Roeker and Dr. Meghan Thompson describe their approach to shared decision making for patients with CLL.

(00:09) Lindsey Roeker:
So over the last decade, we have had development of major classes of drugs that have really revolutionized how we treat CLL. So when I'm meeting a patient and talking to them about their first therapy, there are a few considerations. The first is there is still a minority of patients who might be good chemoimmunotherapy candidates. Typically, we think of these as young, fit patients with mutated IGHV, and we know that these are patients that can have long-term remissions with chemoimmunotherapy. So I have that as part of my discussion.

(00:41) Lindsey Roeker:
So for the vast majority of patients, we are talking about a novel agent-based approach. We have BTK inhibitors that are given as continuous therapies, and we have BCL-2 inhibitor based therapies, which can be given as time limited therapies. These are two classes of agents that have different side effect profiles, different logistics of administration, and really are a different experience for patients. So it's important that we educate them on what to expect with each of these classes.

(01:08) Lindsey Roeker:
So after that frontline therapy, when I'm thinking about their next line of therapy, I really take stock of what they've received before and why did they stop it? So for patients who were on covalent BTK inhibitors, did they stop because of intolerance where we might have lots of different options? Or did they stop because of progression, where the options are really continuing to inhibit BTK, but with a different mechanism, or using a different class of drug.

(01:35) Meghan Thompson:
So I think that's really important, knowing why the patient discontinued the prior therapy. Was it intolerance? Was it progression? And then as a clinician, I'm often faced with that decision and I really take a look at the most recent data, what's out there, what tools are available in terms of treatments. Sometimes it's switching to another target or mechanism of action, different class of drug. And then there are also drugs available that focus on the same target, but in a different way.

What factors do you consider when treating patients with CLL?

Dr. Lindsey Roeker and Dr. Meghan Thompson discuss their thoughts on treatment options for CLL.

BCL-2=B-cell lymphoma 2; BTK=Bruton’s tyrosine kinase; CLL=chronic lymphocytic leukemia; ECOG=Eastern Cooperative Oncology Group; HCP=health care provider; iwCLL=2018 International Workshop for Chronic Lymphocytic Leukemia; PI3K=phosphatidylinositol 3-kinase; R/R=relapsed/refractory; TN=treatment naïve.

References

Shadman M. JAMA. 2023;329(11):918-932.
HealthTree Foundation for Chronic Lymphocytic Leukemia. What is watch and wait for CLL? Accessed August 12, 2024. https://healthtree.org/cll/community/articles/what-is-watch-and-wait-for-cll
Hampel PJ, Parikh SA. [published correction appears in Blood Cancer J. 2022;12(12):172]. Blood Cancer J. 2022;12(11):161.
Jamil A, Mukkamalla SKR. Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560826/
Cheson BD, et al. J Clin Oncol. 2014;32(27):3059-3068.
Lumish M, et al. J Hematol Oncol. 2021;14(1):5.
Terret C, et al. Expert Rev Hematol. 2015;8(3):329-341.
. InformedHealth.org [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. In brief: What are clinical practice guidelines? [Updated 2016 Sep 8]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK390308/
Sun R, et al. Mod Pathol. 2016;29(10):1118-1142.
Ngu H, et al. Am Soc Clin Oncol Educ Book. 2022;42:1-14.
Loh KP, et al. Blood Adv. 2020;4(21):5492-5500.
Lymphoma Action. CLL and SLL. Accessed August 12, 2024. https://lymphoma-action.org.uk/types-lymphoma/chronic-lymphocytic-leukaemia-cll-and-small-lymphocytic-lymphoma-sll#what-is
Campo E, et al. Haematologica. 2018;103(12):1956-1968
Katz SJ, et al. J Oncol Pract. 2014;10(3):206-208.
LUNGevity Transforming Lung Cancer. Shared decision-making. Accessed May 12, 2024. https://www.lungevity.org/research/patient-focused-research-center-patient-force/shared-decision-making
Agency for Healthcare Research and Quality. The SHARE approach: a model for shared decision making. Accessed May 12, 2024.https://www.ahrq.gov/sites/default/files/publications/files/share-approach_factsheet.pdf

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When do patients with CLL need treatment?

iwCLL indications for treatment3,a

Leverage SHARE principles for shared decision making14,16

Related Resources

Downloadable PDFs

How do you approach shared decision making in CLL?

What factors do you consider when treating patients with CLL?

References

Please rate your satisfaction with the content on the following statements:

Please rate your satisfaction with the content on the following statements:

iwCLL indications for treatment^3,a

Leverage SHARE principles for shared decision making^14,16