Treatment tips in CLL

02/20/20 • 22 min

The million-dollar question in the treatment of chronic lymphocytic leukemia (CLL) is what to do after a patient relapses following treatment with venetoclax. Anthony Mato, MD, and Lindsey Roeker, MD, both of Memorial Sloan Kettering in New York, join podcast host David H. Henry, MD, of Pennsylvania Hospital, Philadelphia, to explore the evidence about this question and to review the initial patient work-up and treatment strategies.

In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, discusses patients compliance and how clinician biases can influence compliance.

Practice points:

For patients with CLL with unmutated immunoglobulin variable heavy chain gene (IgVH), novel agents are the first therapy.
Evidence is limited about the best treatment approach after relapse on venetoclax.

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Initial work-up in patients with CLL

The initial work-up for patients with CLL is often fluorescent in situ hybridization (FISH), looking for trisomy 12, as well as deletion of 13q, 17p, and 11q.
Next-generation sequencing is used to look for mutations in TP53 and IgVH mutational analysis is done to recognize whether a patient is mutated.
IgVH-mutated patients tend to respond better to therapy.

When to treat

Henry recommends the “if it bothers you, it bothers me” approach, noting that indications for treatment include fever, chills, night sweats, lumps and bumps in the neck, large liver and spleen, and high creatine.

Progression

If a patient is IgVH unmutated, that takes chemoimmunotherapy combinations off the table, regardless of whether the patient is young or fit. Instead, they are on a pathway to receive a novel agent as first therapy.
The choices for novel agents keep expanding. Some standards include ibrutinib plus or minus obinutuzumab, venetoclax plus obinutuzumab, and acalabrutinib plus or minus obinutuzumab.
Each of these combinations has different adverse event profiles and dose schedules. Patient preferences and comorbidities should drive decision making on novel combinations.

Relapse

The million-dollar question: What is the best treatment following relapse on venetoclax?
The answer is unclear but there are generally two choices: Re-treat with the same regimen or switch to a Bruton’s tyrosine kinase (BTK) inhibitor.
There are limited data on re-treatment and emerging data on BTK inhibitors after venetoclax that points to success.

Disclosures

Dr. Anthony Mato reported research funding from DTRM Biopharma and Gilead; consultancy and research funding from Genentech, Pharmacyclics, TG Therapeutics, Adaptive, Sunesis, AstraZeneca, Abbvie, LOXO, and Johnson & Johnson; and consultancy with Verastem, Acerta, Janssen, and Celgene.

Dr. Lindsey Roeker reported minority ownership interest in Abbvie and Abbott Laboratories, ASH grant funding.

Dr. Henry and Dr. Yurkiewicz reported no relevant financial conflicts.

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For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

Ilana Yurkiewicz on Twitter: @ilanayurkiewicz

In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, discusses patients compliance and how clinician biases can influence compliance.

Practice points:

For patients with CLL with unmutated immunoglobulin variable heavy chain gene (IgVH), novel agents are the first therapy.
Evidence is limited about the best treatment approach after relapse on venetoclax.

* *

Initial work-up in patients with CLL

The initial work-up for patients with CLL is often fluorescent in situ hybridization (FISH), looking for trisomy 12, as well as deletion of 13q, 17p, and 11q.
Next-generation sequencing is used to look for mutations in TP53 and IgVH mutational analysis is done to recognize whether a patient is mutated.
IgVH-mutated patients tend to respond better to therapy.

When to treat

Henry recommends the “if it bothers you, it bothers me” approach, noting that indications for treatment include fever, chills, night sweats, lumps and bumps in the neck, large liver and spleen, and high creatine.

Progression

If a patient is IgVH unmutated, that takes chemoimmunotherapy combinations off the table, regardless of whether the patient is young or fit. Instead, they are on a pathway to receive a novel agent as first therapy.
The choices for novel agents keep expanding. Some standards include ibrutinib plus or minus obinutuzumab, venetoclax plus obinutuzumab, and acalabrutinib plus or minus obinutuzumab.
Each of these combinations has different adverse event profiles and dose schedules. Patient preferences and comorbidities should drive decision making on novel combinations.

Relapse

The million-dollar question: What is the best treatment following relapse on venetoclax?
The answer is unclear but there are generally two choices: Re-treat with the same regimen or switch to a Bruton’s tyrosine kinase (BTK) inhibitor.
There are limited data on re-treatment and emerging data on BTK inhibitors after venetoclax that points to success.

Disclosures

Dr. Lindsey Roeker reported minority ownership interest in Abbvie and Abbott Laboratories, ASH grant funding.

Dr. Henry and Dr. Yurkiewicz reported no relevant financial conflicts.

* *

For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

Ilana Yurkiewicz on Twitter: @ilanayurkiewicz

Previous Episode

When to refer for CAR T-cell therapy

Chimeric antigen receptor (CAR) T-cell therapy is one of the hottest advances in lymphoma treatment, but who should get it and what does the process look like? Allison Winter, MD, of the Cleveland Clinic helps answer those questions on the podcast. She joins Blood & Cancer host David H. Henry, MD, of the Pennsylvania Hospital, Philadelphia, to break down the side effects and look ahead to possible off-the-shelf products.

In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, discusses optimism bias. She recalls a time when a patient’s drive for optimism affected what she told them and whether that was a good or bad thing.

Practice points:

The time to refer a patient for CAR T-cell therapy is at relapse.
CAR T-cell therapy side effects are serious and include cytokine release syndrome and neurotoxicity.

CAR T-cell therapy use in lymphoma

For patients with diffuse large B-cell lymphoma, treatment after relapse typically involves salvage therapy, and if they are chemotherapy-sensitive, autologous transplant.
The time to refer a patient for CAR T-cell therapy (or other clinical trial options) is at the time of relapse.
CAR T cells are currently approved after two lines of therapy.
What is the process for a patient to get CAR T-cell therapy?
- Evaluation by physicians.
- Approval of insurance.
- Collection of the patient’s T cells.
- Shipment of T cells for genetic modification (takes several weeks).
- Reception of genetically modified T cells by patients.
- Administration of lymphodepleting chemotherapy.
- Admission to the hospital for CAR T-cell infusion.
The median time to get CAR T cells is 26 days.
Allogeneic CAR T-cell products (called off-the-shelf) are in the clinical trial stage.
The two major side effects of immunotherapy include cytokine release syndrome and neurotoxicity.

Reference:

Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28; 377:2531-44.

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Show notes by Emily Bryer, DO, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

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For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

Ilana Yurkiewicz on Twitter: @ilanayurkiewicz

Next Episode

Treatment approaches in AML

A diagnosis of acute myeloid leukemia (AML) was once an emergency, requiring immediate treatment. Today, the need to start treatment is still urgent, but many patients can benefit by waiting a few days for testing to reveal a fuller picture of the disease. That’s the advice of James M. Foran, MD, of the Mayo Clinic. He joins Blood & Cancer host David H. Henry, MD, of the Pennsylvania Hospital, Philadelphia, to walk through some patient scenarios and the newest treatment options.

In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about what patients do and do not remember from their visits.

Practice points:

Rapid testing results can drive important choices in the initial treatment of AML.
Adjunctive therapies may improve survival by 7%-20% in appropriate patients.

Although a total work-up may take up to 2 weeks, new research suggests it is feasible to get rapid sequencing/cytogenetic testing and assign treatment within 7 days.

Treatment varies:

Daunorubicin and cytarabine (Vyxeos) are still central treatment strategies, but there may be survival advantages (7%-20% improvement) by adding adjunctive therapies, if indicated. A few are listed below:

Liposomal formulations of daunorubicin-cytarabine (CPX351) can have survival advantages in therapy-related AML or AML with myelodysplastic syndrome (MDS)-related changes.
Gemtuzumab (Mylotarg) may be indicated for core binding factor (CBF) AML.
Midostaurin (Rydapt) may improve survival in patients with FMS-like tyrosine kinase (FLT) 3
Enasidenib (Idhifa) may be indicated in patients with IDH mutations.

Options for elderly patients:

In a recent study, CC 486 (oral azacitidine) showed a significant survival advantage and remission duration in elderly patients with AML. The drug is not yet available but could eventually be a maintenance therapy option for patients who do not go on to transplant.

Azacitidine, plus or minus an IDH2 inhibitor, showed much higher remission rates in elderly patients, but did not translate into a survival advantage.

AML in the outpatient setting:

Many patients with AML are being increasingly managed as outpatients, which ultimately will require a different kind of support infrastructure in our hospitals and clinics.

Show notes by Debika Biswal Shinohara, MD, PhD, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

Dr. Henry and Dr. Yurkiewicz reported having no financial conflicts relevant to this episode. Dr. Foran reported advisory board membership with Pfizer, Jazz Pharma, and Novartis.

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For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

Ilana Yurkiewicz on Twitter: @ilanayurkiewicz