Relapsed/Refractory Patients:

Treatment Options - Pomalyst


Pomalyst®


Overview

 

What is Pomalyst?

Pomalyst® is an oral immunomodulatory agent (IMiD™) that is similar to and Revlimid® (lenalidomide) and Thalomid® (thalidomide) but is more potent.  It is an oral medication.

Pomalyst is also called pomalidomide and is made by Celgene. In the United States, Pomalyst is approved for the use in patients with myeloma who have received at least two prior therapies, including Velcade® (bortezomib) and Revlimid® (lenalidomide) and who have demonstrated disease progression on or within 60 days of completion of the last therapy.

The Multiple Myeloma Research Consortium (MMRC) has played a substantial role in the development of this drug as a partner with Celgene in the early clinical trials establishing its efficacy and continues to sponsor trials evaluating Pomalyst in combination with various myeloma drugs.

How does Pomalyst work?

Pomalyst works in multiple ways to slow or kill myeloma cells. Recently it has been shown in studies the MMRC helped to fund that Pomalyst and other IMiDs bind a protein in myeloma cells called cereblon. This binding triggers myeloma cell death. In some studies higher levels of cereblon are associated with better outcomes after treatment. Pomalyst is also known to stimulate the immune system and to affect the blood vessels and other substances surrounding a tumor (known as the tumor microenvironment) which help to feed the cancer cell's growth.

How is Pomalyst and low-dose dexamethasone taken?

Pomalyst is taken orally at a dose of 2 to 4mg daily for three out of four weeks (days 1-21 of each 28-day cycle). Each Pomalyst capsule should be taken with water. Pomalyst should not be taken with food and should be taken at least 2 hours before or 2 hours after a meal. Dexamethasone is taken at a dose of 40mg weekly. The dose of dexamethasone is reduced to 20mg weekly for patients older than 75 years old.

Typically, aspirin or another blood thinner is taken along with Pomalyst and low dose dexamethasone. 

Pomalyst and dexamethasone are taken for as long as they continue to work to against the myeloma.

What are the possible side effects with Pomalyst and low-dose dexamethasone?

Pomalyst and low-dose dexamethasone is generally well-tolerated. The most common side effects seen in the Phase II study upon which approval was granted were:

  • Fatigue and weakness

  • Low white blood cell counts (neutropenia)

  • Low red blood cell counts (anemia)

  • Gastrointestinal effects (constipation, nausea, or diarrhea)

  • Shortness of breath

  • Upper respiratory infection

  • Back pain

  • Fever

The most common serious side effects seen in the Phase II study were:

  • Low white blood cell counts and fever associated with low white blood counts (febrile neutropenia)

  • Low red blood cell counts

  • Low platelets (thrombocytopenia)

  • Blood clots

If you experience low white blood cell or platelet counts or other serious side effects while receiving Pomalyst, your doctor may adjust your dose. LEARN MORE >

Some patients who received Pomalyst in clinical trials developed blood clots. For this reason, you will also receive aspirin or another blood thinner along with Pomalyst.

Women who are pregnant or who plan to become pregnant must not take Pomalyst. This precaution is due to its similarity to Thalidomide, and some signs of birth defects in animals. A program called has been created (Pomalyst REMS) to prevent exposure to Pomalyst during pregnancy.

  • Doctors and pharmacists must register with the program in order to prescribe and dispense Pomalyst.

  • Patients must register and meet all the conditions of the program in order to take Pomalyst.

What types of patients can benefit from Pomalyst?

Pomalyst has been shown to be effective in patients with relapsed and refractory multiple myeloma following multiple lines of treatment with other available agents, including Velcade and Revlimid.

In addition, Pomalyst is effective in patients with high-risk myeloma as well as those with kidney problems.

How effective is Pomalyst in treating relapsed and refractory multiple myeloma?

Pomalyst was granted approval by the US Food and Drug Administration based on the results of a Phase II trial that evaluated Pomalyst alone and in combination with low-dose dexamethasone. The study included 221 patients with relapsed myeloma who had received an average of 5 previous therapies, were refractory to their last myeloma therapy, and had received both Velcade and Revlimid.

  • This study showed that 33% of patients receiving the combination and 18% of patients receiving Pomalyst alone achieved a partial response or better.

  • The responses lasted a median of 8.3 months in the combination group and 10.7 months in the Pomalyst group.

  • On average, the overall survival was 16.5 months in the combination group and 13.6 months in the Pomalyst group. This is longer than what has historically been seen in patients in whom currently approved novel therapies have failed.

  • Pomalyst-low-dose-dexamethasone was just as effective in patients who had received Revlimid as part of their last treatment and whose myeloma no longer responded to Revlimid or both Revlimid and Velcade.

The combination of Pomalyst and low-dose dexamethasone was compared to high-dose dexamethasone in a Phase III trial with 455 patients with refractory myeloma who had failed therapy with both Velcade and Revlimid, given either alone or in combination.

  • This study showed that patients receiving the combination of Pomalyst plus low-dose dexamethasone lived longer than those receiving high dose dexamethasone.

  • Overall responses rates were 31% with Pomalyst and low-dose dexamethasone versus 10% with high-dose dexamethasone alone.

  • On average, time without progression of myeloma was 4.0 months with Pomalyst and low-dose dexamethasone versus 1.9 months with high-dose dexamethasone alone.

  • The combination was effective in patients with high-risk myeloma and those who previously received Revlimid.

A variety of 3-drug regimens that include Pomalyst have shown promising activity in early-stage trials. For example:

  • In 2 small trials, the combination of Pomalyst, Velcade, and dexamethasone resulted in overall response rates that were higher than historically seen with Velcade, Revlimid, and dexamethasone. However, direct comparisons between these combinations cannot be made as the patient populations were different, and longer follow-up is needed to determine survival.

  • The combination of Kyprolis (carfilzomib), Pomalyst, and dexamethasone resulted in an overall response rate of 70% in a Phase II study, and responses were similar in patients with and without high-risk genetic factors. On average, the time to disease progression was 9.7 months, and overall survival has not yet been reached.

  • The addition of Biaxin® (clarithromycin) doubled the response rate and time to disease progression compared to Pomalyst and dexamethasone alone in a Phase II study in heavily pretreated patients. This combination is referred to as ClaPd.

  • Response rates in a Phase I/II trial of Pomalyst-dexamethasone with or without cyclophosphamide compare favorably with that seen with Pomalyst-dexamethasone alone.

  • The combination of Pomalyst, Doxil, and dex may offer an option for patients who are refractory to or intolerant of Velcade.

 

How is Pomalyst currently being studied in myeloma?

Pomalyst is being evaluated in a number of ongoing clinical trials in relapsed and/or refractory myeloma. For example:

  • A Phase III trial is comparing Pomalyst plus Velcade-low-dose-dexamethasone versus Velcade-low-dose dexamethasone (OPTIMISMM). This trial will enroll 782 patients with relapsed or refractory disease.

  • A Phase II trial is evaluating use of Pomalyst-low-dose dexamethasone as third-line treatment in patients who had previously received Revlimid-dexamethasone as second-line treatment.

  • The use of ClaPd followed by autologous stem cell transplant and Pomalyst maintenance is being compared to continuous CladPd therapy in a Phase II trial.

  • A Phase Ib/III trial is evaluating Pomalyst and dexamethasone with or without the oral proteasome oprozomib (Onyx). This trial has completed enrollment.

Other approved and investigational drugs are being studied in combination with Pomalyst in early clinical trials in relapsed and/or refractory myeloma. Several are listed in the table below.


New Combinations with Pomalyst: Early Studies (Phase I and II)
Treatment: Pomalyst plus... Description/Possible anti-myeloma effect
Istodax® (romidepsin) and dexamethasone Histone deacetylase inhibitor
Dexamethasone with or without Ixazomib (MLN9708, Millennium) Oral proteasome inhibitor
Treanda® (bendamustine) and dexamethasone Chemotherapeutic agent; will include Pomalyst-dex maintenance
ACY-1215 (Acetylon) and low-dose dexamethasone Oral histone deacetylase inhibitor, trial set to begin
Afinitor® (everolimus) and dexamethasone Oral novel agent (mTOR inhibitor); trial set to begin

To find a clinical trial, call 1-866-603-MMCT (-6628) or click here to go to the MMRF Patient Navigator Program.


For more information on Pomalyst, visit www.pomalyst.com.



Reviewed by:
Keith Stewart, M.B.C.H.B.
Mayo Clinic
Scottsdale, AZ