Isatuximab (brand name Sarclisa, and as Sarclisa Escena) is a targeted monoclonal antibody used to treat multiple myeloma.
It binds to the CD38 receptor on the surface of multiple myeloma cells to trigger their destruction.
Isatuximab is administered in combination with standard chemotherapy and corticosteroid regimens.
The FDA has approved it for relapsed or refractory multiple myeloma: Given with pomalidomide and dexamethasone for adults who have received at least one prior line of therapy (including lenalidomide and a proteasome inhibitor).
Given with carfilzomib and dexamethasone for adults who have received one to three prior lines of therapy.
Newly Diagnosed Multiple Myeloma: Given with bortezomib, lenalidomide, and dexamethasone for adults who are ineligible for an autologous stem cell transplant.
Isatuximab is available in two forms:Intravenous (IV) Infusion: Administered directly into the vein. .
Subcutaneous Injection: Administered under the skin, which can be done manually or via an innovative on-body injector (Sarclisa Escena).
Common side effects of isatuximab combinations can include:Decreased white blood cell count (neutropenia), which significantly increases the risk of infection.
Severe systemic allergic/administration reactions and local injection-site reactions
Respiratory tract infections (including pneumonia and bronchitis).
Diarrhea, fatigue, nausea, and muscle/joint pain.
Phase 3 ICARIA-MM trial, showing promising efficacy and safety for isatuximab in combination with pomalidomide and low-dose dexamethasone in relapsed/refractory MM.
It is different from daratumumab, because it has a different isotope for binding.
As a monotherapy, response rates are comparable to what we see with daratumumab.
IT requires a short infusion time and relatively limited pre‑med.
Because it activates compliment to a lesser degree it has a favorable tolerability profile.
The rates of infusion reactions are quite low.
ICARIA trial revealed the combination with isatuximab combined with pomalidomide, showed an impressive response rate in relapsed/refractory patients.
Isatuximab is given typically weekly for the first month, and then can be converted onto every 2 weeks thereafter.
Pomalidomide which was given 3 weeks on and 1 week off.
Over 90% of the patients were refractory to lenalidomide.
Associated, essentially with a doubling of PFS.
There was 12‑month median PFS for the 3 drugs, and a six‑month PFS for the 2 drugs.
There was effectively a doubling of response rate from around 35%, to approximately 60% to 70% in the 3-drug combination.
Infusion reactions were low in terms of incidents.
Seeing a trend in favor of overall survival advantage to 3 drugs over the 2.
The use of isatuximab early in the relapsed/refractory course conferred trend favoring survival.
Approved with addition of isatuximab to the combination of carfilzomib and dexamethasone to treat adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy,.
The anti-CD38 treatment of choice for patients with relapsed or refractory multiple myeloma.
Phase 3 IKEMA trial showed that the triplet reduced the risk of disease progression or death by 45% vs Kd alone in this patient population.
The median progression-free survival had not yet been reached with the isatuximab combination.
No statistically significant difference in objective response rate was observed with the triplet vs the doublet, at 86.6% vs 82.9%, respectively; complete response rates were 39.7% vs 27.6%, respectively
Isatuximab-VRd (bortezomib, lenalidomide, dexamethasone (VRd) as in initial therapy in patients 8 to 80 years of age with newly diagnosed multiple myeloma was more effective than VRd in patients ineligible to undergo transplantation.
Most common adverse events; respiratory tract infection, infusion-related reactions, fatigue. hypertension, diarrhea, pneumonia, dyspnea, and cough
Serious AEs in the isatuximab combination: were pneumonia and upper respiratory tract infections.
The addition of Sarclisa to carfilzomib and dexamethasone reduced risk of disease progression or death by 45%.
The study reinforces the potential for isatuximab to become a standard of care in relapsed or refractory multiple myeloma.