alternative dosing scheme of pomalidomide 4 mg every other day versus pomalidomide 2 mg and 4 mg every day; the pomalternative study

Conditions: Multiple Myeloma in Relapse; Multiple Myeloma; Multiple Myeloma, Refractory

Summary: pomalidomide either as single therapy or in combination with cyclophosphamide, elotuzumab, bortezomib, or daratumumab are effective treatment regimens in relapsed refractory multiple myeloma (rrmm). standard dosing is 4 mg/day during 21 days of a 28-day cycle (21/28). however, a clear dose-response association for pomalidomide in patients with multiple myeloma (mm) is lacking. there is data supporting that a dose of 2 mg/day continuously (28/28) induces fewer side effects while efficacy is preserved, compared to 4 mg/day continuously. the response in patients who received pomalidomide 2 mg per day compared to 4 mg per day was higher, with a longer duration of response. in addition, a randomized phase ii study showed no difference in efficacy between 4 mg (21/28) and 4 mg continuously. these clinical studies support that a dosage of pomalidomide of 2 mg (28/28) is at least comparable with a dosage of 4 mg (21/28). it is not known if 4 mg every other day (eod) is comparable to a dosage of pomalidomide 2 mg (28/28) or 4 mg every day (qd, 21/28). for cost reasons, this is interesting as the costs of pomalidomide 4 mg and 2 mg are comparable. therefore, from a patient and societal perspective, the investigators want to explore if an alternative scheme would be possible by performing a pkpd bio-equivalence pilot study.

pomalidomide either as single therapy or in combination with cyclophosphamide, elotuzumab, bortezomib, or daratumumab are effective treatment regimens in relapsed refractory multiple myeloma (rrmm). standard dosing is 4 mg/day during 21 days of a 28-day cycle (21/28). however, a clear dose-response association for pomalidomide in patients with multiple myeloma (mm) is lacking. there is data supporting that a dose of 2 mg/day continuously (28/28) induces fewer side effects while efficacy is preserved, compared to 4 mg/day continuously. the response in patients who received pomalidomide 2 mg per day compared to 4 mg per day was higher, with a longer duration of response. in addition, a randomized phase ii study showed no difference in efficacy between 4 mg (21/28) and 4 mg continuously. these clinical studies support that a dosage of pomalidomide of 2 mg (28/28) is at least comparable with a dosage of 4 mg (21/28). it is not known if 4 mg every other day (eod) is comparable to a dosage of pomalidomide 2 mg (28/28) or 4 mg every day (qd, 21/28). for cost reasons, this is interesting as the costs of pomalidomide 4 mg and 2 mg are comparable. therefore, from a patient and societal perspective, the investigators want to explore if an alternative scheme would be possible by performing a pkpd bio-equivalence pilot study.

Eligibility criteria:
inclusion criteria: * patients with relapsed/refractory multiple myeloma, who are eligible for a treatment regimen which contains pomalidomide. either monotherapy or in combination with bortezomib, daratumumab, cyclophosphamide, or elotuzumab * patients who received a minimum of two cycles of pomalidomide 4mg every day on day 1-21/28 * age \> 18 years * who performance status 0-3 * written informed consent exclusion criteria: * usage of cyp1a2 inhibitors (e.g. ciprofloxacin, enoxacin, ketoconazole, carbamazepine, fluvoxamine, and grapefruit juice) * renal insufficiency requiring dialysis * significant hepatic dysfunction (total bilirubin \> 330 μmol/l or transaminases \> 3 times normal level) * current smoker * hemoglobin \<6.5 mmol/l * thrombocytes \<100 \*10\^9/l * neutrophiles \<1.5 \*10\^9/l * pregnant patients * female patients who are able to get pregnant and who do not agree to adequate birth control or complete abstinence * male patients who do not agree to adequate birth control or complete abstinence * hypersensitivity to pomalidomide or constituents

Keywords: multiple myeloma pomalidomide pharmacokinetics/dynamics cost-effectiveness