2021 EHA Discovery of New Drugs for Multiple Myeloma

Multiple myeloma (MM) is the second most common hematological malignancy, mainly in elderly patients
.

Although the overall survival of MM patients has been significantly improved in the past few decades, there is still no cure for MM, and most patients eventually relapse
.

The 26th European Hematology Annual Conference (2021 EHA) has been held today.
The editor compiled two early studies on the exploration of new MM drugs at this EHA conference for the reference of readers
.

01S187: Iberdomide+dexamethasone+daratumomab/bortezomib/carfilzomib for the treatment of RRMM patients.
Iberdomide (IBER) is a new oral cereblon E3 ligase modulator (CELMoD) and proteasome inhibitor (PI) or anti-CD38 monoclonal antibody combination has significant synergistic anti-tumor and immune stimulation effects
.

The CC-220-MM-001 study is an ongoing phase 1/2 study, which aims to evaluate the maximum tolerance of IBER in combination with different drugs in patients with relapsed/refractory multiple myeloma (RRMM) in an independent cohort Dose, recommended phase 2 dose (RP2D), safety and preliminary efficacy
.

In the Iberdomide+dexamethasone+daratumomab (IberDd) cohort and Iberdomide+dexamethasone+carfilzomib (IberKd) cohort on day 1-21 (28 days as a cycle), and in the Iberdomide+ dexamethasone Methsone+bortezomib (IberVd) cohort was given an increasing oral dose of IBER on days 1-14 (21 days as a cycle)
.

Dexamethasone was given weekly in all 3 cohorts
.

As of December 14, 2020, 34 patients received IberDd treatment, 24 patients received IberVd treatment, and 7 patients received IberKd treatment
.

All patients had poor effect on the last treatment plan.
The median previous treatments of the IberDd, IberVd and IberKd groups were 4.
0 (2-12), 5.
5 (1-14) and 6.
0 (2-8), respectively
.

The IBER dose range is 1.
0-1.
6 mg
.

The median follow-up time of the IberDd, IberVd and IberKd groups were 3.
9 (0.
1–20.
7), 5.
5 (1.
2–18.
0), and 5.
1 (3.
5–15.
7) months, respectively, and the median treatment cycles were 4.
0 (1-21) and 7.
5, respectively (1-24) and 5.
0 (3-16)
.

Safety: The most common adverse events (TEAE) during grade 3-4 hematology treatment: IberDd group: neutropenia (63%), anemia (28%), leukopenia (28%) and lymphocytes Decrease (25%); IberVd group: neutropenia (29%), thrombocytopenia (25%); IberKd group: lymphopenia (57%) and neutropenia (43%)
.

The incidence of grade 3-4 non-hematological TEAEs in the three cohorts was low
.

Efficacy: IberDd group: The overall response rate (ORR) was 41% (12/29: 1 case of strict complete remission [sCR], 2 cases of complete remission [CR], 2 cases of very good partial remission [VGPR], 7 Cases with partial remission [PR]), the clinical benefit rate (CBR) was 52%, and the disease control rate (DCR) was 86%
.

IberVd group: ORR was 58% (14/24: 2 CR, 5 VGPR, 7 PR), CBR was 67%, and DCR was 92%
.

IberKd group: ORR was 57% (4/7: 1 sCR, 2 VGPR, 1 PR), CBR was 57%, and DCR was 86%
.

The IberDd and IberVd regimens are effective for patients with refractory daratumomab and bortezomib, respectively
.

The median duration of remission in the IberDd, IberVd, and IberKd groups were 4.
1 weeks (4.
0–12.
0), 3.
6 weeks (3.
0–13.
1), and 4.
1 weeks (4.
1–8.
1), respectively.
The median duration of remission was unreached, 63.
3, and unreached, respectively.
Reach
.

The study shows that RRMM patients (including daratumomab and bortezomib refractory patients) who have undergone multi-line therapy in the past receive IberDd, IberVd and IberKd treatments with controllable safety and considerable efficacy
.

These results support the further exploration of treatment options for MM containing IBER
.

02S188: Selinexor + carfilzomib + dexamethasone once a week for the treatment of MM patients who have received multi-line therapy.
Selinexor (SEL) is a new type of oral selective nuclear export inhibitor, and low-dose dexamethasone ± bortezo The combined use of rice has been approved by the FDA for use in previously treated MM patients
.

The investigators conducted a phase 1b/2 study to determine the maximum value of weekly SEL + carfilzomib + dexamethasone (XKd) for MM patients who have received multi-line therapy (excluding refractory carfilzomib) Tolerated dose, RP2D, safety and efficacy
.

As of January 4, 2021, a total of 27 patients were recruited: 18 (67%) were male, the median age was 71 years (50-76), and the median previous treatment was 4 (1-8)
.

All 27 patients had previously received bortezomib treatment.
In addition, 26 patients (96%), 19 patients (70%), 18 patients (67%) received nalidomide, pomalidomide, and dare Toyuumab
.

Most patients (67%) received three types of drug therapy (PI, immunomodulator [IMiD] and anti-CD38 monoclonal antibody), and 44% of patients were triple refractory
.

Nine patients (33%) were quadruple refractory cases of bortezomib, lenalidomide, pomalidomide, and daretuzumab
.

Common adverse events related to hematology treatment (TRAE; total, ≥ grade 3) include thrombocytopenia (74%, 56%), anemia (59%, 19%), and neutropenia (30%, 7%)
.

Non-hematological TRAEs include nausea (67%, 4%), fatigue (52%, 7%) and anorexia (52%, 4%)
.

RP2D was identified as SEL 80mg QW, carfilzomib 56mg/m2 QW and dexamethasone 40 mg QW
.

As of February 3, 2021, the ORR was 78% (21/27), of which 5 patients (19%) achieved CR, 8 (30%) patients achieved VGPR, and 8 (30%) patients achieved PR
.

The median progression-free survival (PFS) was 23.
7 months
.

Among the 18 patients who had previously received daratumumab treatment, the ORR was 67%, and the median PFS was 23.
7 months
.

Among the 9 patients with four-fold refractory treatment, the ORR was 67%, and 4 patients achieved VGPR (44%)
.

Among the MM patients who have received multi-line therapy, the ORR of the weekly XKd regimen is 78%, and the deep remission (≥VGPR rate is 48%), and the overall PFS is 23 months
.

All AEs are controllable and manageable
.

These research data further support the role of XKd regimen in previously treated MM patients
.

Reference source: 1.
Sagar Lonial, IBERDOMIDE (IBER) IN COMBINATION WITH DEXAMETHASONE (DEX) AND DARATUMUMAB (DARA), BORTEZOMIB (BORT), OR CARFILZOMIB (CFZ) IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY MULTIPLE MYEL (RRMM).
2021 EHA Annual Meeting.
Abstract S187.
2.
Cristina Gasparetto, ONCE WEEKLY SELINEXOR, CARFILZOMIB, AND DEXAMETHASONE (XKD) IN CARFILZOMIB NONREFRACTORY MULTIPLE MYELOMA (MM) PATIENTS.
2021 EHA Annual Meeting.
Abstract S188.
progress