Kyprolis Combo Shows Promise for Newly Diagnosed, Transplant-eligible Patients

Kyprolis Combo Shows Promise for Newly Diagnosed, Transplant-eligible Patients

A triple regimen composed of Kyprolis (carfilzomib), thalidomide, and dexamethasone, given before and after high-dose chemotherapy and autologous stem cell transplant, is safe and highly effective for the treatment of newly diagnosed multiple myeloma, results of a Phase 2 clinical trial show.

The study, “Phase 2 Study Of Carfilzomib, Thalidomide, And Low-Dose Dexamethasone As Induction And Consolidation In Newly Diagnosed, Transplant Eligible Patients With Multiple Myeloma, The Carthadex Trial,” was published in the journal Haematologica.

Survival rates for patients with multiple myeloma have significantly improved over the last few decades. However, the majority of patients will eventually progress, which highlights the need for new therapeutic approaches.

One of the treatment options for patients with newly diagnosed multiple myeloma is high-dose melphalan (a chemotherapy) combined with autologous stem cell transplantation — a procedure where a patient’s blood stem cells are collected before the high-dose chemotherapy and transplanted afterward.

Patients who undergo a stem cell transplant are also given induction and consolidation therapy in an attempt to deepen the responses to the transplant. Induction therapy is the first phase of treatment — before the chemotherapy and transplant. Its goal is to reduce the number of cancer cells. Consolidation therapy is given after the transplant. Its goal is to kill any cancer cells that may remain in the body.

Studies have shown that response to induction and consolidation therapy in patients undergoing a stem cell transplant is associated with an improvement in progression-free survival (length of time without disease progression) and overall survival.

Therefore, it is important to select the most beneficial induction and consolidation therapy in order to achieve a maximum response after the transplant.

Standard induction treatment consists of a triple regimen including a proteasome inhibitor, an immunomodulatory agent (which regulates the immune system), and dexamethasone (an immunosuppressant).

Proteasomes are cellular complexes that work to break down old or faulty proteins. Thus, treatments preventing the proteasome from working cause the accumulation of toxic proteins within cells, making them excellent tools for killing a cancer.

Generally, the combination of the proteasome inhibitor Velcade (bortezomib), thalidomide, and dexamethasone is the most commonly prescribed regimen in transplant-eligible newly diagnosed patients. However, Velcade is associated with higher rates of a complication called polyneuropathy (nerve pain), which often leads to treatment discontinuation.

Amgen‘s Kyprolis is a selective proteasome inhibitor that has been approved in the United States and Europe for the treatment of patients with relapsed or refractory myeloma.

While not yet approved for newly diagnosed patients, the treatment causes a much lower incidence of polyneuropathy than Velcade, and recent trials in newly diagnosed patients showed high response rates.

To further investigate the replacement of Velcade with Kyprolis, researchers initiated a Phase 2 dose-escalation trial — called Carthadex (NTR2422) — of Kyprolis in combination with thalidomide and dexamethasone.

The study included 111 newly diagnosed multiple myeloma patients, eligible for high-dose chemotherapy and an autologous stem cell transplant, who were given one of four Kyprolis doses — 27 mg/m2, 36 mg/m2, 45 mg/m2, and 56mg/m2.

In a prior study, researchers had already reported data from the first three cohorts, showing that the Kyprolis combination was well-tolerated. In this study, researchers report the results of the four dose groups with a longer follow-up.

Results indicated that, after induction therapy, 93% of patients responded to treatment, a number that increased to 94% after the stem cell transplant and remained at 94% after the consolidation therapy.

Complete responses (the disappearance of all cancer signs) also increased from 18% after induction therapy to 31% after the transplant, and to 63% after the consolidation therapy.

While responses increased with the Kyprolis dose, researchers found that the time patients lived without disease worsening (median 58 months) was not affected by the treatment’s dose. Overall survival was 83 months (nearly seven years) and was also not affected by dose.

Among severe or life-threatening adverse events, 11% of patients experienced infections, 8% respiratory disorders, 9% skin disease, and 9% vascular disease. Only one patient reported experiencing severe polyneuropathy.

Therefore, “carfilzomib, thalidomide, and dexamethasone as induction and consolidation treatment after high-dose melphalan and autologous stem cell transplantation is highly efficacious and safe in transplant-eligible patients with newly diagnosed multiple myeloma,” researchers concluded.

Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
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Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
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Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.

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