Updated May 7, 2026
Edward Ratner, MD
Summary: Starting treatment for CLL / SLL requires a complex decision-making process. There are several well-established choices, but they differ in multiple ways. This essay describes a set of issues to consider in a deliberative process to transition from monitoring CLL / SLL to active treatment. Fortunately, whatever decision is made will likely achieve the goal of many years of feeling well with suppression, and possibly eradication, of CLL / SLL from the bloodstream.
Introduction
Most people with CLL / SLL have had a journey similar to mine. In 2012, the diagnosis came a complete surprise. After reassurance from my oncologist that I wouldn’t need treatment for many years (if ever), I began a journey of routine monitoring, with heightened anxiety in the days before each follow-up appointment. What has changed since then, when chemoimmotherapy was the only approved treatment for CLL / SLL, there are now several excellent choices for first-line targeted therapy. This essay describes the deliberate process I used to make a complicated decision about how to start my treatment regimen.
I am a physician with expertise in internal medicine, geriatrics, and palliative care used to caring for others having a serious illness. This dual role, as a clinician and patient, is both a blessing and a curse. It is easier for me than most people to imagine the worst-case scenarios. It has led me to search the medical literature for an association of every ache or pain I have to my CLL. My background also allows me to make my CLL treatment decisions with the wisdom gained from advising others with various medical dilemmas. I now seek to share my decision-making process to help others with CLL / SLL.
What were my options
When my oncologist recommended we plan for treatment, he ordered a new analysis of my CLL cells, called a FISH test, and a TP53 and 17p determination. These results were used to guide therapy recommendations. This is the basis for the CLL Society’s mantra, “Test before you treat.”
At the time I started treatment in late 2022, my options were the combination of a BCL2 inhibitor (BCL2i) such as obinutuzumab and an anti-CD20 monoclonal antibody (anti-CD20 mAb) such as venetoclax versus a covalent Bruton Tyrosine Kinase-inhibitor (cBTKi), such as ibrutinib, acalabrutinib or zanubrutinib. Since then, additional combinations of these three types of drugs have been approved. Detailed information about these drugs can be found here. An excellent source for up to date guideline for care of CLL / SLL can be found on the Web site for the National Comprehensive Cancer Network (www.nccn.org), which includes a patient-friendly version.
In late 2025, data from a head-to-head comparison of three treatment options (continuous ibrutinib OR fixed-duration venetoclax-obinutuzumab or venetoclax-ibrutinib was published. A summary of that study can be found here. The key difference in therapy approaches were a time-limited (typically 1-year) combination of drugs versus continuous (i.e. life-long or until problems arise) use of a single drug. Up to about a quarter of people on such initial treatments couldn’t stay on them as long as intended. The different treatments have different side effects, but problems significant enough to require hospitalization are rare (<10%). Infection is more common in combination therapy. All three options have similar and high rates of success (over 70%) at keeping the CLL / SLL under good control for at least several years.
In summary, the three options reported in the CLL17 study have fairly similar likelihoods of both good and adverse results but have different patient experiences, types of risks and time commitments. There is no right or wrong choice. This makes this decision among the most difficult because it depends upon predicting the future and valuing intangible things like the number of hours receiving medical care or the effort to take medicine reliably.
An option not available to me, but good for many people with CLL / SLL is enrollment in a research trial. Advantages include close oversight of care, reduced costs, and even stipends paid to enrollees. Disadvantages include extra appointments and tests, the potential need for travel to a study site, and loss of some control while enrolled. However, enrollment in a trial also provides the satisfaction of helping advance knowledge for others’ benefit. To find clinical trials for CLL worldwide, go to www.clinicaltrials.gov, a U.S. government Web site, or ask your oncologist or a medical librarian at your hospital to search for you. There are a number of studies are now enrolling new patients examining novel combinations of approved drugs and new drugs with potential for higher success or fewer side effects. For example, one study with sites across the U.S. and in many other countries, is evaluating a newer BTKi, Nemtabrutinib (MK-1026) vs. approved BTKi choices.
Decision-making process
There is a spectrum of ways to make a healthcare decision. At one extreme, a patient can delegate a decision to the clinicians or a family member. In other words, I could have asked my oncologist what to do and simply followed his instructions. Prior generations of doctors were very comfortable making decisions on patients’ behalf under the paternalism principle. In some cultures, the delegation of health care decisions to a family member or community leader is common. This is ethically acceptable, but only if a patient wants to take that approach. On the other extreme, a patient can bring their decision to the doctor and ignore any contrary advice from the oncology team. This, too, is ethically acceptable if the patient can provide a reasoned justification. Finally, the most common decision-making model is somewhere in-between, as a collaboration between the patient and health care team, typically including at least the oncologist, nurses, and pharmacist. In this model, the team presents options. It helps the patient decide, or the patient makes a request but explores other options with clinicians. My approach was a variation of this, using the Cold War phrase “Trust but Verify.” First, my oncologist recommended a well-established and proven treatment protocol. I then did extensive research about this, which included reading the original published studies, professional society guidelines, recent research presentation slide decks, and even FDA package inserts. I also got a second opinion from another oncologist and spoke with others who opted for this treatment in a CLL Society support group.
Goals or “What Matters”
Before choosing therapy for CLL / SLL, consider the trade-offs in doing everything possible to eradicate the CLL / SLL versus enjoying every day as much as possible. For people near death from other causes or who cannot make decisions due to brain disease, it could be appropriate to forgo treatment directed at the CLL cells. Instead, there are approaches to manage and reduce symptoms, accepting the progression of the disease and death. In more typical circumstances, consider risks of death or serious illness due to the treatment compared to the likelihood of success of treatment. For example, the combination therapy may have greater risk of infection than continuous BTKi. That risk is offset by a chance to have no CLL / SLL cells detectable at completion. Another trade-off is that combination therapies are more time intensive in the first six months than a BTKi alone but requires no daily effort after the first year.
There are other aspects to “what matters” that need to be considered in choosing a CLL / SLL treatment. These include how you would feel about the cost of care (to you or society) and about taking medicines several times per day long-term, possibly life-long. In addition, simultaneous management of other illnesses and/or responsibilities, such as work or caregiving, may influence CLL / SLL-related decisions. Ideally, oncology teams have the time and expertise to explore patient values and preferences. My experience required significant self-reflection, discussions with my family and feedback from my CLL support group members about these topics.
What might come next?
All treatment options for CLL / SLL have a risk that they won’t be tolerated or that the CLL / SLL will become resistant to that treatment. Therefore, deciding what to use for initial treatment should consider what might be done next. Fortunately, there are now second- and third-line treatment options regardless of what is chosen first. The NCCN guideline cited above provide examples of this. For example, some initial time limited treatments can be repeated if the CLL / SLL relapses some years later, with an alternative to switch to continuous BTKi. Overall health or competing life priorities may impact decisions about how much risk and time to invest in first-line therapy versus deferring risk and time commitment to later in life, if needed. As in a game of chess, thinking about future moves may influence current decisions. Discussing contingency plans with your oncology team before deciding where to start is wise.
Consider when to start
Long-standing guidelines in CLL / SLL care specify criteria to begin treatment. These standards allow some people with CLL / SLL to complete their life without ever needing treatment, and delay treatment for years after diagnosis for most everyone else. Unlike most cancers, there is no evidence that early treatment adds enough benefit to recommend it. However, studies of people most likely to need treatment within a few years of diagnosis, such as those with certain genetic markers, are ongoing, with one such study widely available as described here. The criteria to start treatment are based upon CLL affecting the production of red blood cells or platelets, causing spleen or lymph node discomfort, or having significant general symptoms such as weight loss, persistent and consistent night sweats, or fatigue. A rapid rise in the number of lymphocytes, even without symptoms, may also be a reason to start treatment.
Once meeting criteria seems likely within months, planning for treatment should begin; only rarely is treatment suddenly urgent. A typical process may be a recommendation for treatment at one oncologist visit, with a timeline to decide which treatment and make necessary arrangements at a follow-up visit some months later. Sometimes, symptoms diminish or labs improve between visits, and treatment is postponed.
Once a firm decision to start treatment is made, scheduling becomes essential. Treatment may require an increased frequency of medical appointments or cause side effects, so other obligations or vacation plans should be considered before picking a start date. Addressing general health and preventive care, including dentistry, may be better before starting treatment, especially if the therapy could delay healing or recovery from procedures. Health insurance issues may affect timing, such as expected changes in coverage (e.g., starting Medicare or switching plans). If medical appointments require travel, seasonal weather may factor in choosing a start date. Because they are so expensive, CLL / SLL treatments often require prior authorization/approval from the health insurer, which may delay start dates if not sought as soon as a decision is made. For protocols that require infusions, scheduling those appointments may require some lead time, especially to get a specific day of the week. Finally, some oncologists may only be in your preferred office on certain days and have busy schedules, so that a start date may depend on the oncologist’s availability. If significant CLL / SLL symptoms are affecting quality of life, advocacy to overcome potential delays may be needed.
Consider cost
The retail price of the treatments for CLL / SLL is typically over $10,000 per month or per infusion session. For patients on Medicare or some other government plans, the out-of-pocket costs in 2026 are capped at $2,100 per year. For those on commercial insurance plans, cost may have an impact on a choice of therapy, although patient assistance programs can offset some or all costs. Being on a BTKi for years will likely have lifetime higher out-of-pocket costs (as well as societal costs) than a 1-year protocol with combination therapy.
For some people, it may be financially better or worse to start therapy late one year versus early the following year, as many insurance programs reset copay caps annually. Before beginning treatment, check with your insurance company about copays and out-of-pocket costs. Then, at annual open enrollment, consider options to see if savings are possible in different plans. For Medicare plans, this can be done at: www.medicare.gov.
Consider where to receive care
To get treatment for CLL / SLL, four organizations/sites are required: 1) a hematology/oncology program to prescribe treatment, 2) a clinic/infusion center to administer and oversee treatment, 3) one or more labs to monitor treatment, and 4) a specialty pharmacy to dispense oral medication. All may be part of one organization at one location, but commonly patients organize multiple sites for these various roles, due to geography or insurance issues.
With rapidly progressing research and numerous treatment choices, I encourage people with CLL / SLL to seek input on starting therapy from an oncology team focused on CLL / SLL or lymphomas. A general oncologist who starts therapy for only a few patients with CLL / SLL per year cannot easily advise you on all of the factors that may influence the choice of treatment. Getting the opinion of someone more expert is almost always possible, often by videoconference. The CLL Society can help connecting with an expert through the Expert Access program. There is research evidence that care from CLL / SLL experts prolongs survival.
The combination therapy protocols require many more visits than during the prior years of watch and wait. Convenience may be an important factor in deciding where to receive such care. It is common to have treatment oversight nearby, even if the treatment recommendation came from a clinic far away.
Another part of care while on treatment is lab monitoring. That does not have to occur at the oncologist’s office, but timely (e.g., within hours) reporting of results to the oncologist may be necessary, especially with venetoclax. Having labs done at a primary care medical offices probably can’t deliver that speed. Most hospital-based lab can serve this purpose and fax results to an oncologist. For example, it may be appropriate to have labs done at a local hospital the day before an infusion appointment if there is a several-hour trip to the oncology center’s infusion clinic. Similarly, the protocol for escalating venetoclax doses may include labs in the morning after a dose adjustment to monitor for side effects. Again, a local hospital lab may be the best location for that test rather than returning to a distant oncologist’s office or staying near there overnight.
Oral medications for CLL / SLL are delivered by one of a handful of specialty pharmacies that dispense such expensive drugs through package delivery services. They have pharmacists and nurses who provide education about the medications and follow-up calls to monitor for side effects. Unlike community pharmacies, they will call the patient to schedule refills. Check with your prescription drug insurer to get the list of options and enroll with a specialty pharmacy as early as possible. Many insurers are flexible on out-of-network pharmacies from which the first month of therapy is dispensed, but it is easier to start with a specialty pharmacy that is within network that to have to switch.
Consider who will help
The prior sections highlight the complexity of the treatment process for CLL / SLL. Almost every patient will need some help. This assistance may include offering to drive to appointments, providing companionship during infusions, accepting delivery of medications, helping manage medications (e.g., set-up or reminders), managing a calendar of appointments, or managing bills and insurance. The infusion therapy protocols will require more help; a lack of reliable family members or friends may point toward all-oral treatment choices.
Accept your choice
Once a treatment choice is made, it is best to fully accept that decision rather than worrying about whether it was the right choice. As stated above, there is no right or wrong choice. Problems may arise, but it cannot be known what would have happened if the other option had been made. The goal is to get through the year of time limited therapy or to take the BTKi until it stops working. A therapy change can occur if side effects can’t be addressed with a dose adjustment or other medications. Since there are options, don’t accept significant discomfort or disability while on a treatment protocol.
Celebrate success
There are many points in the course of therapy that justify celebration. That includes: completing the six cycles of infusion therapy, completing the first year of treatment, normalization of blood tests, shrinkage of lymph nodes, a good measurement of residual disease, and every anniversary (on a BTK inhibitor or in remission) after that. Plan to share the news with friends and family and to celebrate with those who have helped along the journey.
What I chose
Every individual’s circumstances are different, so my choice, after careful deliberation, may not be the best for you. I have favorable CLL markers (e.g., mutated IGHV, 13q deleted, and no TP53 genetic alteration) and have good kidney function. I live 90 miles from my CLL team located at Mayo Clinic. I have commercial insurance. With my oncologist’s advice and concurrence from a University of Minnesota CLL specialist, I chose to start my treatment with obinituzamab and vententoclax (O + V), driving to Rochester, MN for my care. In retrospect, the travel wasn’t terrible, despite some extra night away due to snowstorms.
2 years Later
I am pleased to report continued full remission of my CLL, with normal blood tests. The 1-year course of treatment had its challenges, requiring 2 uneventful nights in the hospital after side effects of the first infusion, dose reduction of venetoclax for low white blood counts, and a month of intermittent diarrhea from norovirus. A coughing form of asthma that developed during treatment was eventually cured with an inhaler. I am hoping for a long remission.
Disclaimer: The content is solely the responsibility of the author and does not necessarily represent the official views of the VA or the United States Government.
