Brian Koffman, MDCM (retired), MS Ed:
I’m Dr Brian Koffman, a retired family doctor and a patient with CLL myself. I’m also the Cofounder, Chief Medical Officer, and Executive Vice President of the nonprofit CLL Society, which is dedicated to the unmet needs of the CLL community. We are a physician‑curated, patient‑facing organization that helps support, educate, advocate on behalf of patients with CLL and do research in the area of CLL. Today, I will be discussing disease knowledge, frequent concerns, and common misconceptions about CLL among patients with this malignancy.

HCPs should be sensitive to the impact of diagnosis and the cognitive dissonance that can arise when patients are diagnosed with CLL. Unlike the situation decades ago, when many patients were symptomatic at the time of diagnosis, today most patients are diagnosed inadvertently. For example, a patient may have an abnormal blood count that is detected when they arrive for an elective surgery or go in for a routine check. These patients may have been feeling fine, but now they’ve been told they have cancer, and not only is it a chronic leukemia—but it’s also incurable. It is a shock to the system to suddenly go from being asymptomatic to a diagnosis of CLL. Understanding how CLL is diagnosed and how an unexpected diagnosis changes a patient’s life is critical in helping your patients navigate this significant life change.

Brian Koffman, MDCM (retired), MS Ed:
At the 2018 American Society of Clinical Oncology Annual Meeting, my colleagues and I⁶ presented data from a large online and paper-based survey of 1147 US patients with CLL that sought to assess their perspectives on diagnosis and treatment. Almost one half of patients reported being told that they “have the ‘good’ cancer” or that they would “die with CLL, not from CLL.” HCPs believe they are helping patients with these statements. However, the feedback we’ve gotten from patients is that this wording sets up a cognitive dissonance. As HCPs, we understand that there is a large range of cancer diagnoses and—as more than 40% of patients were told—if we had to choose a cancer, this would be the one we’d want. But patients aren’t aware of that spectrum, and attaching the word “good” to a cancer diagnosis makes no sense and can seem dismissive and disturbing. Instead, HCPs can be more sensitive and have a more nuanced discussion with patients about how CLL can progress and how some patients do extremely well with the disease.

Patients also can have very different emotional responses to being told that their management plan is active observation with no treatment. These responses fall into 2 broad categories. The first category is anxiety, with patients thinking: “Are you kidding me? Are you a real doctor? I’ve just been diagnosed with cancer, and you’re telling me that you’re not going to do anything about it?” The “watch and wait” approach for CLL is very different from the approach to breast, colon, and other cancers, where early detection and treatment are critical. Active observation can be a challenging time for the patient, and 56% of surveyed patients reported feeling extremely anxious when told about it.

At the other end of this spectrum, 52% of the patients reported feeling relief: “Well, that’s great. I don’t need any treatment—that’s the best news ever.” And many patients are just confused. Although 91% of patients said their doctor explained why therapy was not warranted, 38% reported confusion. It’s critical that treating HCPs understand how patients may react to their cancer diagnosis and help them understand why we’re not actively treating them.

Nichole Fisher, RN, BSN:
A patient who has just received a CLL diagnosis may be thinking about several things, including: “I feel fine, what do you mean I have cancer? If I have cancer, why am I not getting treated?” We need to make sure we’re educating the patient on why we watch and wait when it comes to CLL, including what monitoring we will be doing, with associated lab work and office visits. Another common misperception is: “I’m young. Isn’t this mainly an old person’s disease?” The average age of a patient with CLL is approximately 70 years, but this disease is not exclusive to older patients and can occur in younger patients.

Because most patients do not present with any symptoms before diagnosis, it also is important to educate about the signs and symptoms that might indicate the disease has progressed to a point where we need to initiate treatment. These include the classic B symptoms, such as fever, chills, night sweats, and unexplained weight loss. Others are count based, such as disabling fatigue with an elevated lymphocyte and/or white blood cell count. Swollen lymph nodes, repeat infections, or increased bleeding or bruising may warrant further workup, as well.

Anthony Perissinotti, PharmD, BCOP:
We let patients know up front that their disease is generally not curable, just to set the stage and help them understand that this is something they likely will be managing for the rest of their lives. We talk about how that might influence which therapy we select now vs therapies we might select later.

Brian Koffman, MDCM (retired), MS Ed:
Reports of patients’ understanding of various aspects of CLL—including disease characteristics, indications for therapy, prognostic testing, and disease progression and potential complications—reveal that, in every category, patients are getting more information via self‑directed education than directly from their HCPs.⁶ As HCPs, we already know that there’s a third person in the room whenever we see a patient: the Internet. We have to be cognizant of that reality and help our patients access reliable sources of information to find out more about their disease. In CLL, these include the CLL Society, the Leukemia & Lymphoma Society, and others.

Brian Koffman, MDCM (retired), MS Ed:
The COVID-19 pandemic has reminded us that patients with CLL are immunocompromised due to the nature of their disease and their treatment. As such, it is critical to get patients fully vaccinated and provide other protections against infections as early in the disease course as possible. It’s also important to make sure they have all the relevant cancer screenings due to their suppressed immunity.

Brian Koffman, MDCM (retired), MS Ed:
Next, we’ll look at the considerations involved in leaving behind active observation and preparing to treat a patient. Several different treatment options are available, and specific testing is important before treatment to guide therapy decisions. For more information on selecting first-line therapy for patients with CLL, please review this short video or module.

Nichole Fisher, RN, BSN:
Data from the informCLL registry study of 840 patients who received treatment in a community practice setting suggest HCP knowledge and practice gaps surrounding prognostic testing for hematologic and genetic markers that can help drive treatment decisions, including TP53, IGHV, and 17p mutation status (NCT02582879).⁷ Fewer than one third of newly diagnosed patients with CLL in this registry were tested for risk‑associated mutations, and there was a gap in HCP understanding surrounding how marker testing results should guide the selection of treatment for high‑risk patients. Patients with del(17p) typically have a shorter watch and wait period, may respond poorly to chemoimmunotherapy, and often have more rapid disease progression and poorer survival than patients without del(17p). However, approximately one third of patients in the informCLL registry who were found to have del(17p) or TP53 mutations received chemoimmunotherapy, which is not recommended.⁷

Anthony Perissinotti, PharmD, BCOP:
I also think it’s important to sit down with patients and educate them on the available treatment options to reduce their knowledge gaps and misperceptions about different regimens. There are many effective treatment options. As HCPs, we can let our patients know our personal preferences of the major treatment approaches, but ultimately I think it’s best to tell patients all the pros and cons of each approach and compare and contrast them. That gives patients all the information they need to help them make a treatment decision.

There’s a misperception that oral therapies are less toxic than IV medication. Certainly the newer oral therapies aren’t as toxic as fludarabine, cyclophosphamide, and rituximab (FCR) and bendamustine and rituximab in certain senses, but they still have toxicities that our patients need to know about. They have to know what to expect and when they should reach out to us if certain toxicities arise.

Brian Koffman, MDCM (retired), MS Ed:
We have done research to understand patients’ preferences when making treatment decisions. At the 2021 American Society of Hematology Annual Meeting and Exposition, my colleagues and I⁸ presented results from an online survey of 608 patients with CLL about the key factors in CLL therapy choices. We were pleased to find that, in a forced ranking, one half of patients rated overall survival as the most important factor in choosing therapy. It might be surprising to some that 3 of 10 patients ranked not having chemotherapy as being extraordinarily important. Other factors we might expect to be important, such as reaching undetectable measurable residual disease (MRD) or having minimal lab visits, were the most important factor to fewer than 10% of patients.

When we asked patients to describe the importance of various factors in terms of their therapy, 96% of patients ranked overall survival as very important or somewhat important, with 93% of those patients saying it was very important. Because nearly all CLL therapies are palliative at this time, postrelapse options are a significant aspect of care, and patients seemed to be aware of that, with 99% of those who participated in the survey indicating that having a good option if they relapse was very or somewhat important to them. And again, not having chemotherapy was very or somewhat important to 93% of patients.

Two thirds of patients thought it was very important to have the ability to reach undetectable MRD. Surprisingly, limited duration of treatment was less significant, with only 46% ranking that as very important. Only one third of patients ranked minimal lab work and office visits as very important.

Brian Koffman, MDCM (retired), MS Ed:
Involvement in clinical trials can vary widely across patient populations. In the 2018 patient survey on CLL treatment, we noted a marked disparity between what happens when a patient sees a CLL expert vs a general hematology oncologist.⁶ Only 9% of patients reported being asked by a general hematology oncologist to consider a clinical trial, and 5% agreed. When treated at a teaching center with a CLL expert, however, 51% of patients were asked about a clinical trial, and 43% agreed.

Of note, a significantly higher number of patients older than 65 years of age were asked and agreed to enter a clinical trial (37% and 30%, respectively) compared with those younger than 65 years of age (28% and 20% of patients).

Nichole Fisher, RN, BSN:
These findings have been confirmed by the American Society of Hematology and the Leukemia & Lymphoma Society, who report that the national rate of cancer clinical trial enrollment is 5% to 8%. This has substantial implications for the speed of treatment innovation and access to quality care. 

Brian Koffman, MDCM (retired), MS Ed:
Let’s look at an example of a patient’s treatment journey. Mark presented to his primary care provider with enlarged lymph nodes, which were watched for a long time before he was sent to a hematologist. Mark had a lymph node biopsy by an otolaryngologist and was originally diagnosed with small lymphocytic lymphoma. He was working with a local hematologic oncologist but was advised to get a second opinion and started doing some of his own research, including on the CLL Society website. His local hematologist had recommended FCR therapy, which was a standard of care at that time, but they had not done any testing before treatment to look for del(17p) or TP53 abnormalities. Mark educated himself and suggested getting genetic testing. He was found to have del(17p) CLL, so chemotherapy would have been suboptimal. I think Mark’s story emphasizes the importance of patient self-advocacy and education. As HCPs, more and more we are seeing patients coming in with awareness of this relatively rare disease and a clear picture of which therapies they want.

Mark sought a second opinion at an academic medical center and turned down the FCR treatment. He is now on the CAPTIVATE trial of first-line ibrutinib and venetoclax and has undetectable MRD 2 years after stopping his therapy.

Nichole Fisher, RN, BSN:
This patient had to advocate for himself based on the information he researched online after an initial recommendation of chemoimmunotherapy. His efforts changed his entire course of treatment, because the genetic and molecular testing he requested showed that the suggested treatment likely would have been suboptimal for him. After seeking a second opinion, he began treatment with a different combination that has worked very well. Encouraging patients to learn about their disease, genetic markers, treatment options, and adverse events can help guide their treatment decisions.

Anthony Perissinotti, PharmD, BCOP:
I noted 3 things about this case. First, I commend this patient on his self-advocacy. I do think it’s important to get multiple opinions. Even within our practice, we make many of our treatment decisions as a group—especially in more challenging cases—consulting other hematologists, nurse practitioners, or pharmacists. Getting additional opinions from other places, as this individual did, also can be helpful. That choice dramatically changed his outcome. Patients with del(17p) CLL who receive chemotherapy historically have lived for only approximately 3 years, whereas those who receive treatment with our novel therapies can live about as long as patients without the deletion.

The second important message here is that we have to continue to educate ourselves on the proper management of CLL, as well as the biomarkers and molecular markers for which we should be testing. Even a few years ago, relatively few community institutions were sending off tests for mutations in immunoglobulin heavy chain or del(17p), for example. Recent advocacy efforts—whether via patients, educational programs, or community outreach—appear to be affecting a shift toward increased testing for appropriate molecular markers. As we saw in this case, that testing can dramatically change a patient’s outcome.

The third aspect of this case is patient enrollment on clinical trials, which is really the only way we can move forward in the treatment of CLL. Continuing to prescribe the standard of care will improve our use of that standard of care, but it won’t help us learn how to better treat CLL.

Brian Koffman, MDCM (retired), MS Ed:
In summary, we need to remember that, for most patients, the diagnosis of CLL comes as a shock. Many patients come into the office, feeling well, for some routine procedure or examination and leave with the diagnosis of an incurable cancer. On top of that, they are told that we’re not going to do anything about it—we’re just going to watch it.

The patient may suddenly start noticing symptoms. Maybe they now feel lymph nodes they ignored or that weren’t bothering them before, or they are suddenly more fatigued or more anxious. These are serious issues that need to be addressed. In addition, the COVID-19 pandemic has called into clear focus the need for us to address the immunocompromised state of these patients in terms of both infection protection and cancer screening.

We have learned that patients can be quite sophisticated when it comes to treatment. They can bring their own preferences to the table, which may align with our main interests in some cases and not in others. They may be interested in therapies that provide the best overall survival, but they also may be opposed to therapies that involve chemoimmunotherapy. It’s important to get your patient’s perspective to understand what they want.

This reminds us of the importance of shared decision-making. Patients bring to the table their personal needs and priorities, and we can form a good bond through clear communication, careful listening, and thoughtful choice of words to describe this chronic condition. By considering their preferences and making sure they have appropriate educational sources, you can guide patients through what we hope will be a very long, successful, and low‑impact journey with this chronic incurable cancer.

Now, let’s return to the question from earlier in the activity.