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Standardization of High Sensitivity Minimal Residual Disease Monitoring in Multiple Myeloma: An Experience in Tertiary Cancer Centre

In Clinical Lymphoma Myeloma & Leukemia
By: Subramanian P.
Contributor(s): Chatterjee G | Ghogale S | Gokarn A | Gudapati P | Deshpande N | Yajamanam B | Patkar N | Amare P | Inamdar N | Punatar S | Bagal B | Jain H | Sengar M | Khattry N | Gujral S | Tembhare P.
Material type: materialTypeLabelArticlePublisher: 2019Description: .Subject(s): CLR 131 | Phospholipid ether | Radiotherapeutic | Generation flow cytometry (NGF) In: Clinical Lymphoma Myeloma & Leukemia Vol. 19, no. (Suppl10), p. e357.Summary: primary objective is to determine safety and tolerability of CLR 131 as a single or fractionated dose. Secondary objectives are to determine the recommended Phase 2 dose, schedule, and therapeutic activity in RRMM. Eligibility includes progressive disease, permitting patients with relapsed or refractory disease to at least 1 PI and 1 IMiD, and prior ASCT. In the cohort presented, CLR 131 is administered as a 37.5 mCi/m2 dose fractionated as 2, 30 minute intravenous infusions (18.75 mCi/m2 on day 1 and day 7) with 40 mg dex orally qw for 12 weeks. Adverse events (AEs) are graded by NCI-CTCAE v4.03. Results: Data on 4 subjects enrolled to cohort 6 (37.5 mCi/m2 fractionated CLR 131) is presented here. Median age for cohort 6 was 66 years (range 59-83) and included 2 males and 2 females. The majority of subjects (3/4) were high risk by cytogenetics, median bone marrow plasma cell involvement was 25% (range 10- 60%). Number of prior therapies averaged 4 (range 3-6). 50% of subjects had prior ASCT and none had prior radiation therapy. One subject was dual class refractory, 1 was quad-refractory and 2 were penta-refractory, including being refractory to daratumumab. The overall response rate for cohort 6 was 50% - 2 subjects achieved a partial response (PR); the other 2 subjects achieved a minimal response (MR). One subject with a PR experienced a 61% reduction in k FLC and the other a 68% reduction in l FLC; 1 subject with an MR had a 39.1% reduction and the other a 48% reduction in m-protein. Both subjects with a PR and 1 subject with an MR were high risk by cytogenetics. CLR 131 has been well tolerated. There have been no reported deep vein thrombosis, pulmonary embolisms and no treatment emergent deaths. Grade 3-4 treatment emergent AEs occurring in over 25% of subjects have been neutropenia (50%), anaemia (75%) and thrombocytopenia (100%);with an average 2 weeks to recoveryfrom nadir. Fatigue (grade 1- 2) and ECG changes (grade 1) have also been noted. Three subjects entered with anemia and 1 also had leukopenia. As no DLTs were seen, dose escalation continues. Conclusions: CLR 131 represents a first in class targeted radiotherapeutic for RRMM. These data suggest that RRMM including high-risk patients can experience meaningful clinical benefit from treatment with CLR 131 with an acceptable and expected safety profile in the fractionated dose cohorts. Based upon this encouraging activity in late line RRMM patients, this dose of CLR 131 is being further evaluated in a larger population in a Phase 2 trial.
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Articles Articles Tata Memorial Hospital
Available AR19679

Abstract presented at 17th International Myeloma Workshop, Sept.12-15, 2019

primary objective is to determine safety and tolerability of CLR 131 as a single or fractionated dose. Secondary objectives are to determine the recommended Phase 2 dose, schedule, and therapeutic activity in RRMM. Eligibility includes progressive disease, permitting patients with relapsed or refractory disease to at least 1 PI and 1 IMiD, and prior ASCT. In the cohort presented, CLR 131 is administered as a 37.5 mCi/m2 dose fractionated as 2, 30 minute intravenous infusions (18.75 mCi/m2 on day 1 and day 7) with 40 mg dex orally qw for 12 weeks. Adverse events (AEs) are graded by NCI-CTCAE v4.03. Results: Data on 4 subjects enrolled to cohort 6 (37.5 mCi/m2 fractionated CLR 131) is presented here. Median age for cohort 6 was 66 years (range 59-83) and included 2 males and 2
females. The majority of subjects (3/4) were high risk by cytogenetics, median bone marrow plasma cell involvement was 25% (range 10- 60%). Number of prior therapies averaged 4 (range 3-6). 50% of subjects had prior ASCT and none had prior radiation therapy. One subject was dual class refractory, 1 was quad-refractory and 2 were penta-refractory, including being refractory to daratumumab. The overall response rate for cohort 6 was 50% - 2 subjects achieved a partial response (PR); the other 2 subjects achieved a minimal response (MR).
One subject with a PR experienced a 61% reduction in k FLC and the other a 68% reduction in l FLC; 1 subject with an MR had a 39.1% reduction and the other a 48% reduction in m-protein. Both subjects with a PR and 1 subject with an MR were high risk by cytogenetics. CLR 131 has been well tolerated. There have been no reported deep vein thrombosis, pulmonary embolisms and no treatment emergent deaths. Grade 3-4 treatment emergent AEs occurring in over 25% of subjects
have been neutropenia (50%), anaemia (75%) and thrombocytopenia (100%);with an average 2 weeks to recoveryfrom nadir. Fatigue (grade 1- 2) and ECG changes (grade 1) have also been noted. Three subjects entered with anemia and 1 also had leukopenia. As no DLTs were seen,
dose escalation continues.
Conclusions: CLR 131 represents a first in class targeted radiotherapeutic for RRMM. These data suggest that RRMM including high-risk patients can experience meaningful clinical benefit from treatment with CLR 131 with an acceptable and expected safety profile in the fractionated dose cohorts. Based upon this encouraging activity in late line RRMM patients, this dose of CLR 131 is being further evaluated in a larger population in a Phase 2 trial.

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