1) Welcome to the next installment of our key #oncology meeting highlights via #accredited #tweetorials from @onc_ce, your new (& only) home for the latest education from #experts on #cancer care. #Physicians #nurses #pharmacists #PAs and #NPs all earn 0.5h CE/#CME by following!
2) We now continue highlighting key data on #multiplemyeloma from @ASH_hematology 2021 (#ASH21). Our expert author is Dr. Suzanne Lentzsch @SLentzsch from @columbiacancer. She will provide recaps of exciting new trials!
3) These #ASH21 summaries on the latest on #multiplemyeloma from @onc_ce & its companion website http://www.oncologytweetorials-ce.com are supported by an educational grant from Abbvie. Content is intended for #healthcare providers. Faculty disclosures are listed at http://www.oncologytweetorials-ce.com/disclosures/.
4) #ASH21 was a hybrid meeting last December, featuring the best basic scientists and clinicians working in #HEMATOLOGY & #ONCOLOGY. We are going to highlight some of the new drugs and drug combinations advancing the care of Relapsed/Refractory Multiple Myeloma #RRMM.
5) For starters, here’s my take on multiple #BCMA x CD3 #Bispecific T-Cell Engagers/Antibodies trials from #ASH21:
— #MagnetisMM-1: Phase 1/2 Study of #Elranatamab
— Phase 1 Study of #REGN5458
— #MajesTEC-1: Phase 1/2 Study of #Teclistamab
— Phase 1b Study of #TNB383B
6) First up, #MagnetisMM-1 https://clinicaltrials.gov/ct2/show/NCT03269136, a study of #Elranatamab given SC. Prior #BCMA treatment was permitted. Data from priming cohort and escalation were presented at #ASH21. See interview w/author Moshe Yair Levy, MD, of @TexasOncology at https://www.targetedonc.com/view/magnetismm-1-shows-promise-of-elranatamab-in-relapsed-refractory-myeloma.
7) #Elranatamab (PF-06863135) is a bispecific antibody (IgG2a) targeting the B-cell maturation antigen (#BCMA) on #MM cells & #CD3 on T cells➡️activate an immune response. SQ administration allows higher doses than IV administration without ⬆️incidence of #AEs.
8) Abstract at https://ash.confex.com/ash/2021/webprogram/Paper152984.html. In the escalation cohort (n=20), across a median follow-up of 12.5 months, 75% (3/4) of patients with prior BCMA-directed therapy achieved response including 1 sCR and 2 VGPR . . . and 100% (4/4) of patients assessed were MRD negative.
9) In the priming cohort (n=20), median f/u was 7.5mos, & elranatamab monotherapy SQ had a manageable safety profile for patients with #RRMM. Confirmed ORR was 69% at the rec'd dose of 1000 μg/kg Q1W. 70% (7/10) of patients with prior BCMA-directed therapy achieved response.
10) MagnetisMM-1 attracted lots of #SoME attention at #ASH21, with posts from @AuclairDan, @Rfonsi1, @ninashah33, our own faculty @DrOlaLandgren,a nd of course @MM_Hub, among others. See https://twitter.com/AuclairDan/status/1470536721594994691 & https://twitter.com/DrOlaLandgren/status/1470538944169320448 to share the excitement!
12) This Phase 1 efficacy study ➡️responses across all dose levels, with a trend for higher response rates at higher doses. Study showed a 75% ORR and 58% ≥VGPR with REGN5458 200–800 mg. Among all responders, 86% achieved ≥VGPR, 43% ≥CR
13) For safety, REGN5458 showed an acceptable & manageable safety/tolerability profile. CRS was reported in 38% of the pts; most events were Gr 1, occurred w/in the 1st 2 wks, & resolved w/in 1 day. No correlation between CRS & dose observed. Abstract at https://ash.confex.com/ash/2021/webprogram/Paper144921.html.
14) @smbenlazar @Abdallah81MD & @mtmdphd called out these results during #ASH21, calling them "promising" and "early, deep, and durable," such as at https://twitter.com/mtmdphd/status/1456679882247876610. Big news! Want a podcast from the presenter? Go to https://www.oncologytube.com/v/40491?channelName=ASHReport_5f6a1d25488df while you get ur #CME here!
15) So while we're talking #bispecific antibodies, here's a quick knowledge✔️. Which of the following might NOT describe a bispecific antibody?
a. two binding sites
b. directed at two antigens
c. naturally occurring antibodies
d. directed at 2 epitopes on same antigen
16) Mark your best answer and return TOMORROW for the answer and to see what other studies will be highlighted from #ASH21 for #RRMM. And while you’re thinking about it, FOLLOW US NOW! @MyelomaTeacher @JillZitzewitz @Razan_Mohty @jmikhaelmd @IMFmyeloma @HadidiSamer @theMMRF
17) Welcome back! I am @SLentzsch and you are earning CE/#CME while we hit some of the many #RRM highlights from #ASH21. My colleagues @Bethfaiman @DrOlaLandgren & @mpdrc are bringing their own highlights here to @onc_ce too! 👏to @ninashah33 @Transplant_Doc @jmsheld9
18) Yesterday's poll? If you didn't answer, scroll back up to tweet # 15, and vote before you read ⤵️. Bispecific antibodies are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. So which option was INcorrect?
19) Choice C, because naturally occurring antibodies typically only target one antigen.
20) So now we move on to another BCMA x CD3 #Bispecific Antibody being studied in #RRMM: #Teclistamab, in the #MajesTEC1 trial from Philippe Moreau, MD of @CHUnantes. Hear his take at https://t.co/qVA7O93t8z
21) The median treatment duration was 5.9 months.
77 patients (46.7%) received ≥6 months of treatment, and no patients had a teclistamab dose reduction. Abstract at https://ash.confex.com/ash/2021/webprogram/Paper147915.html.
22) Overall response: at a median follow-up of 7.8 months (range: 0.5–18):
— ORR of 62.0%
— Median time to first response: 1.2 months
— MRD negativity rate 24.7% at 10(exp -5)
23) For #safety, Teclistamab was well tolerated; no patients required dose ⬇️.
The most common AEs were low grade CRS, except for one Gr 3 event which resolved without discontinuation
ICANS events were rare, were all Gr 1/2, and resolved without discontinuation
24) And finally, wrapping up the BCMA x CD3 T-cell engaging #bispecific antibody studies from #ASH21, we had the phase 1 study of #TNB383B in #RRMM who have received at least 3 prior lines of therapy. Abstract at https://ash.confex.com/ash/2021/webprogram/Paper150757.html.
25) This study was presented by @myelomatips of @WakeCancer. Key design features included
— IV administration (1–2 hours)
— Fixed (as opposed to weight-based) dosing
— Q3W schedule
— Permitted intrapatient dose-escalation to 60 mg
26) TNB-383B was well tolerated at all Q3W doses administered, with a manageable CRS rate & a low incidence of cytopenias. ORR of 81% was observed at doses ≥40 mg. This promising efficacy of TNB-383B Q3W regimen will be further explored
27) So let's move on to a new combination of #Dartumumab with #Teclistamab (BCMA) vs #Talquetamab (GPRC5D) for #RRMM. At #ASH21 we had a Ph 1b study of that comparison. Abstract at https://ash.confex.com/ash/2021/webprogram/Paper148723.html.
28) My (@SLentzsch) interpretation (part 1):
–Combination of tal or tec + dara has no overlapping toxicity
— Up to 55% patients experienced CRS, most Gr 1-2, w/median onset of 2d, 2d duration
— Promising ORR (60-100%) in these heavily pre-treated patients
29) Part 2:
Responses were observed in both CD38–exposed and –refractory patients
These data support tal or tec + dara as a novel immunotherapy-based approach for the treatment of patients with #RRMM
32a) Conclusions from the update (Part 1):
— At median f/u ~2 years pts tx'd w/cilta-cel showed durable & deepening responses
— ORR remained at 98%, with sCR rates higher at a median of ~2 years than at median of ~1 year (83% vs 67%)
32b) Part 2:
— 2-year PFS and OS rates were 60.5% and 74.0%, respectively
— Cilta-cel has a manageable safety profile with no new safety signals observed with longer follow-up
Oncologists: Save this slide. Note the high single agent response rates. The future looks good.”
35) Abstract https://ash.confex.com/ash/2021/webprogram/Paper145572.html, presented by Sham Mailankody of @sloan_kettering.
36) We see a manageable safety profile with low-grade & reversible neurotoxicity, no #GvHD.
14% of patients with AEs of potential low-grade neurotoxicity
Low use of tocilizumab 23% and steroids 14%
30 (70%) patients experienced Gr3+ neutropenia
3 Gr5 infections
37) As @DrRakeshPopat pointed out on Twitter from #ASH21, there is concern with this approach of potential reactivation of what viruses, due to Flu/Cy/anti-CD52 conditioning?
Mark your answer before you scroll ⤵️!
38) It's d–both CMV and parvo. But nonetheless, there was encouraging efficacy seen with additional patients at DL3.
In the 320 million CAR+ cell dose group, 17 patients (71%) achieved an overall response rate (ORR).
11 (46%) were VGPR+, of those 6 (25%) were CR/sCR
39a) My summary of the benefits of Allo Car:
— ALLO-715 UNIVERSAL is the first allogeneic anti-BCMA CAR T study to demonstrate safety & substantial efficacy in #MM
“Off-the-shelf” AlloCAR Ts have potential to address significant unmet need in pts w/rapidly progressive disease
39b) and . . .
— No bridging therapy required
Median time from enrollment to start of therapy of 5 days
40a) In summation for this #tweetorial:
(a) several Bispecific T-Cell Engagers (#BITEs) are in clinical trials with high ORR 60-80%; winner is unclear
(b) Combination of BITES with #Daratumumab as a steroid free combination is safe and promising
(c) CAR-T Cell Treatment results in durable responses but production capacity reduces availability
(d) Allo CAR-T cells – off the shelf – might overcome production problem
(e) ALLO-715 with ALLO-647 is well tolerated with low-grade CRS, low-grade reversible neurotoxicity, no GvHD, & manageable safety
(f) 71% ORR and 46% VGPR+ with 320 million cell dose comparable to approved autologous CAR T therapy
(g) 8.3 months median durability of response, but high rate of Gr 5 infection is a concern
41) Overall, though, #ASH21 brought us great new data on #RRMM. And you just earned 0.5h CE/#CME by sharing this discussion with me @SLentzsch. Now go to https://oncologytweetorials-ce.com/RRMM_BITES_CART and claim your credit. And FOLLOW US NOW for more from #ASH21!