POMALYST®, in com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone, provides a new medication option for patients living with multiple myeloma

Toronto, ON (Press Release) – Celgene Inc. announced today that Health Canada has approved a POMALYST® (poma­lido­mide)-based triplet com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone. This is a new treat­ment option for patients with multiple myeloma (MM) who have received at least one prior treat­ment regi­men that in­cluded REVLIMID® (lena­lido­mide).

POMALYST® is an oral medication taken daily and is indicated, in com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone, for the treat­ment of adult patients with MM who have received at least one prior treat­ment regi­men that in­cluded lena­lido­mide.^1,2

"The treat­ment landscape for multiple myeloma has sig­nif­i­cantly changed over the years. New treat­ment options like this POMALYST®-based triplet com­bi­na­tion allow patients and their physicians to work together to find the best early-line treat­ment regi­men," says Dr. Reece, Princess Margaret Cancer Centre. "In the pivotal clin­i­cal trial, OPTIMISMM, we saw the POMALYST®-based triplet com­bi­na­tion im­prove and provide a sustained pro­gres­sion-free survival for multiple myeloma patients who were exposed to, and for the most part refractory to lena­lido­mide. This is im­por­tant, as over the last few years lena­lido­mide has be­come a standard of care in front-line treat­ment of multiple myeloma in Canada and until OPTIMISMM, the patient pop­u­la­tion exposed or refractory to lena­lido­mide in front line was not well studied. The POMALYST®-based triplet com­bi­na­tion is a pos­i­tive step for­ward in the treat­ment journey for multiple myeloma patients and their loved ones."

MM is an in­creas­ingly prevalent blood cancer originating from bone marrow plasma cells.³ In Canada, the number of patients living with the dis­ease is on the rise, with eight Canadians diag­nosed each day.⁴

"Multiple myeloma is a complex dis­ease which can impact each patient dif­fer­en­tly," says Martine Elias, Executive Director, Myeloma Canada. "It is en­cour­ag­ing to see how new treat­ment options, like the POMALYST®-based triplet com­bi­na­tion, suc­cess­fully treat Canadian myeloma patients."

Health Canada's approval of the POMALYST®-based triplet com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone is based on OPTIMISMM, the first pro­spec­tive­ phase 3 trial, in­clud­ing 559 MM patients, to eval­u­ate a POMALYST®-containing triplet regi­men in patients.⁵ Patients participating in this trial were all pre­vi­ously treated with REVLIMID® and the majority, 70 per cent, were REVLIMID® refractory.^6,7 All patients had received 1-3 prior antimyeloma regi­mens and dem­onstrated dis­ease pro­gres­sion on or after the last ther­apy.⁸

Patients who received the POMALYST®-based triplet com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone in the clin­i­cal trial had a sig­nif­i­cantly longer pro­gres­sion-free survival (PFS) of 4.1 months more than those who received only bor­tez­o­mib and dexa­meth­a­sone (median PFS 11.2 months versus 7.1 months, re­spec­tive­ly).^9,10

About Multiple Myeloma

MM is a life-threatening blood cancer char­ac­ter­ized by tumor proliferation and sup­pres­sion of the immune sys­tem.11,12 It is a rare but deadly dis­ease – around 2,900 people are diag­nosed with MM in Canada and 1,450 Canadians die from the dis­ease each year.¹³ The typical MM dis­ease course in­cludes periods of symp­tomatic myeloma followed by periods of remission, and eventually, the dis­ease be­comes refractory (non-responsive).¹⁴ While all MM patients may ex­peri­ence dif­fer­en­t symp­toms during and after treat­ment, patients may also ex­peri­ence physical issues.¹⁵ These may in­clude bone com­pli­ca­tions, anemia, in­fec­tions, kidney damage, high blood cal­cium and other blood com­pli­ca­tions, osteo­necrosis of the jaw, side effects of medication, as well as bone pain, nerve pain and neu­rop­athy.¹⁶ MM patients may also ex­peri­ence emotional health issues, with 40 per cent of cancer patients experiencing depression or anxiety.¹⁷

About OPTIMISMM

OPTIMISMM is the first phase 3 trial designed to compare the safety and efficacy of a POMALYST®-based triplet com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone versus only bor­tez­o­mib and dexa­meth­a­sone as an early line of ther­apy in patients with re­lapsed or refractory multiple myeloma (with 1-3 prior regi­mens of ther­apy) and prior REVLIMID® exposure, in­clud­ing REVLIMID®-refractory patients.

This multi-center, inter­na­tional, open-label, ran­dom­ized phase 3 clin­i­cal trial in­cluded 559 patients (281 patients in the POMALYST®-based triplet com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone arm and 278 in the bor­tez­o­mib and dexa­meth­a­sone arm). Demographic, base­line, and prior dis­ease char­ac­ter­istics were generally well bal­anced be­tween the two treat­ment arms. All patients had prior treat­ment with REVLIMID®, with the majority being REVLIMID® refractory (71 per cent in the POMALYST®-based triplet com­bi­na­tion arm versus 69 per cent in the bor­tez­o­mib and dexa­meth­a­sone arm) and 70 per cent versus 66 per cent, re­spec­tive­ly, were refractory to their last treat­ment. Median follow-up was 16 months.

Results from OPTIMISMM showed that patients receiving the POMALYST®-based triplet com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone treat­ment achieved a sig­nif­i­cantly longer PFS than those in the bor­tez­o­mib and dexa­meth­a­sone treat­ment arm (11.20 months versus 7.10 months, re­spec­tive­ly [HR 0.61, p= < 0.0001; 95 per cent CI: (0.49-0.77)]), reducing the risk of dis­ease pro­gres­sion by 39 per cent in the POMALYST®-based triplet com­bi­na­tion arm. In an exploratory sub-group analysis of patients with one prior line of ther­apy, median pro­gres­sion-free survival with the POMALYST®-based triplet com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone was 20.73 months versus 11.63 months with bor­tez­o­mib and dexa­meth­a­sone (HR 0.54; 95 per cent CI: 0.36, 0.82).

Patients were stratified based on age (< 75 years old versus 75 years old), number of prior anti-myeloma regi­ments (1 vs. > 1) and β2-microglobulin levels ( 3.5 to < 5.5 mg/L versus > 5.5 mg/L). Patients were ran­dom­ized 1:1 to receive the POMALYST®-based triplet com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone or bor­tez­o­mib and dexa­meth­a­sone. In 21-day cycles, patients received POMALYST® 4 mg on days 1-14 (POMALYST®-based triplet com­bi­na­tion arm only); bor­tez­o­mib 1.3 mg/m2 on days 1, 4, 8 and 11 for cycles 1-8 and on days 1 and 8 for cycles 9 and onwards; and dexa­meth­a­sone 20 mg/day (10 mg if aged > 75 years) on the days of and after receiving bor­tez­o­mib treat­ment.

About Celgene's Immunomodulatory Drugs

IMiD® agents are Celgene's pro­pri­e­tary small molecule, orally avail­able com­pounds for the treat­ment of some blood cancers. IMiD® agents are hypothesized to have multiple mech­a­nisms of action. They have been found to en­hance T cells and (NK) cell-mediated immunity. In addi­tion to immuno­modu­la­tory properties, IMiD® agents are hypothesized to have tumoricidal and antiangiogenic activity. Celgene's portfolio of IMiD® agents have be­come a foundation of multiple myeloma research, with a growing number of studies exploring these com­pounds as com­bi­na­tion partners across a range of settings of the dis­ease.

About POMALYST® (poma­lido­mide)

POMALYST® in com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone is indicated in the treat­ment of adult patients with MM who have received at least one prior treat­ment regi­men that in­cluded lena­lido­mide. It belongs to a group of drugs called immuno­modu­la­tory drugs (IMiDs®).

About Celgene

Celgene is an integrated global bio­pharma­ceu­tical com­pany engaged primarily in the discovery, devel­op­ment and com­mer­cial­iza­tion of novel ther­a­pies for the treat­ment of cancer and inflammatory dis­eases through gene and protein reg­u­la­tion. For more in­for­ma­tion, please visit the com­pany's website at www.celgene.ca.

Indications and Clinical Use:

POMALYST® in com­bi­na­tion with dexa­meth­a­sone and bor­tez­o­mib is indicated in the treat­ment of adult patients with MM who have received at least one prior treat­ment regi­men that in­cluded lena­lido­mide.

POMALYST® in com­bi­na­tion with dexa­meth­a­sone is indicated for patients with multiple myeloma for whom both bor­tez­o­mib and lena­lido­mide have failed and who have received at least two prior treat­ment regi­mens and have dem­onstrated dis­ease pro­gres­sion on the last regi­men.

Geriatrics (> 65 years of age):

Concomitant admin­istra­tion of dexa­meth­a­sone may in­crease the risk of in­fec­tion, particularly pneu­monia; dexa­meth­a­sone dosing may need to be reduced or interrupted in case of in­fec­tion. Reduce dexa­meth­a­sone dose by half in patients >75 years of age.

Contraindications:

• Pregnant women and women at risk of becoming pregnant
• Breastfeeding women
• Male patients unable to follow or comply with the required con­tra­cep­tive measures
• Hypersensitivity to POMALYST®, thalido­mide, lena­lido­mide or to any ingredient in the for­mu­la­tion or component of the con­tainer

Controlled Distribution Program:

Available only through a controlled distribution pro­gram called RevAid®

Serious warnings and precautions:

• POMALYST® should be admin­istered under the supervision of a qualified physician ex­peri­enced in the use of cancer chemotherapeutic agents.
• Pregnancy: Potential for human birth defects, stillbirths, and spontaneous abortions
• Hematologic: Neutropenia and thrombo­cyto­penia
• Infections, in­clud­ing fatal cases
• Venous thromboembolism: Deep vein thrombosis (DVT) and pul­mo­nary embolism (PE)
• Hepatic: Hepatotoxicity, in­clud­ing fatal cases
• Hepatitis B virus reactivation, in­clud­ing fatal cases
• Severe dermatologic reac­tions: Stevens-Johnson syn­drome, toxic epider­mal necrolysis (TEN) and drug reac­tion with eosinophilia and sys­temic symp­toms (DRESS), in­clud­ing fatal cases
• Tumour lysis syn­drome, in­clud­ing fatal cases

Other Relevant Warnings and Precautions:

• Cardiovascular disorders
• Second pri­mary malig­nan­cies
• Immune reac­tions: Use in patients with active hepatitis A, B, or C in­fec­tion; hypersensitivity reac­tions (angioedema, urticaria)
• Interstitial lung disease
• Neurologic: Possible im­pair­ment of mental and/or physical abilities; periph­eral neu­rop­athy
• Use in hepatic im­pair­ment or renal im­pair­ment
• Monitoring and Laboratory testing required
• Combination treat­ment with bor­tez­o­mib; consult bor­tez­o­mib Product Monograph prior to initiating treat­ment

For More Information:

Please consult the Product Monograph at pomalystpm.ca for im­por­tant in­for­ma­tion relating to adverse reac­tions, drug inter­actions and dosing in­for­ma­tion. The Product Monograph is also avail­able by calling 1-877-923-5436.

References:

1. POMALYST® Product Monograph. Celgene Inc. Accessed July 2, 2019.
2. POMALYST® Product Monograph. Celgene Inc. Accessed July 2, 2019.
3. Myeloma Canada. What is multiple myeloma? https://www.myelomacanada.ca/en/about-multiple-myeloma/what-is-myeloma. Accessed June 3, 2019.
4. Myeloma Canada. What is multiple myeloma? https://www.myelomacanada.ca/en/about-multiple-myeloma/what-is-myeloma. Accessed June 3, 2019.
5. POMALYST® Product Monograph. Celgene Inc. Accessed July 2, 2019.
6. POMALYST® Product Monograph. Celgene Inc. Accessed July 2, 2019.
7. POMALYST® Product Monograph. Celgene Inc. Accessed July 2, 2019.
8. POMALYST® Product Monograph. Celgene Inc. Accessed July 2, 2019.
9. POMALYST® Product Monograph. Celgene Inc. Accessed July 2, 2019.
10. POMALYST® Product Monograph. Celgene Inc. Accessed July 2, 2019.
11. Palumbo A, et al. N Engl J Med. 2011;364:1046-1060.
12. Pratt G, et al. Br J Haematol. 2007; 38(5):563-79.
13. Canadian Cancer Society. Statistics. https://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/statistics/?region=qc Accessed June 3, 2019.
14. Hulin C et al. Leuk Res. 2017; 59: 75–84. 2
15. Canadian Cancer Society. Multiple myeloma – Supportive care for multiple myeloma. https://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/supportive-care/?region=on. Accessed June 27, 2019.
16. Myeloma Canada. Multiple Myeloma Patient Handbook. https://www.myelomacanada.ca/pixms/uploads/serve/ckeditor/myeloma_canada_patient_handbook_10_2017-2.pdf. Accessed June 27, 2019.
17. Myeloma Canada. Multiple Myeloma Patient Handbook. https://www.myelomacanada.ca/pixms/uploads/serve/ckeditor/myeloma_canada_patient_handbook_10_2017-2.pdf. Accessed June 27, 2019.

Source: Celgene.