Talha Badar
@TalhaBadarMD
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Faculty @MayoCancerCare Alumni @MDAndersonNews Specialised in treating leukemia & myeloid disorder. Interest in ALL, TP53m MN & Germline predisposition syndrome
Joined December 2011
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Last Seen Profiles
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American Journal of Hematology | Blood Research Journal | Wiley Online Library
1/ Happy to share latest paper from our
#COMMAND
real-world consortium; one of the largest RWD looking at outcome of Ph+ ALL pts in the contemprary era. 🧵
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8
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#weekend_review
#AML
#leusm
1/ Overview of AML induction strategies!
#MedTwitter
#hemoncfellows
#hemonctrainees
2
52
169
Germline mutations (ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, and TP53) should be excluded as NGS-MRD markers.
DNMT3A, TET2, and ASXL1 can be found in age-related CH and should be excluded from MRD.
FLT3 KIT, and RAS; should be best used with additional MRD markers.
#AML
1
53
150
Distinguishing AML from MDS: a fixed blast percentage may no longer be optimal
@BloodJournal
AML/MDS-EB2 distinction had no effect OS or EFS! ELN risk, HCT, Age, PS, sAML bigger determinants! By late
#ElihuEstey
et al.
#leusm
#mdssm
3
41
138
TP53 mutation in therapy-related myeloid neoplasm defines a distinct molecular subtype ➡️ No diff in OS; t-MDS & t-AML with single or multi-hit TP53➡️ TP53m VAF<10%; OS similar to TP53wt. Excellent work by Drs Devendra Hiwase & Mithun Shah
@MayoCancerCare
2
39
132
#weekend_review
#MDS
#mdssm
Treatment landscape for low-risk MDS in one slide!
#MedTwitter
#hemTwitter
#hemonctrainees
3
35
138
#weekend_review
#ALL
#blinatumomab
#Inotuzumab
🧵
1/ Introduction to B-cell ALL, risk stratification and treatment algorithm for
#hemonc_fellows
#MedTwitter
#hemonctrainees
3
33
125
#weekend_review
1/7 Role of allogeneic stem cell transplantation in Ph+ve ALL? 🧵 👇🏽
#leusm
#ALL
Outcome of Ph+ve ALL has significantly improved with TKI combinations and not considered high risk disease anymore 👇🏽
3
30
118
Excited to share our review in
@BloodJournal
!!
@MRLitzow
#Dr_Selina_Luger
#ALL
#leusm
#immunotherapy
Incorporation of immunotherapy into frontline treatment for adults with B-cell precursor acute lymphoblastic leukemia.
4
21
121
Management of ALL in adults: 2024 ELN recommendations from a European expert panel
Take home message: Rx modification based on MRD status is crucial for better outcome! # leusm
#ALL
1
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113
# Weekend review
1/6 Differentiation syndrome (DS) with targeted therapies for myeloid malignancies
DS characterized by non-infectious related fever, weight gain sec to third spacing (pleural/pericardial effusion) and renal insufficiency.
Historically, known to occur with
5
36
112
#weekend_review
#AML
#leusm
Continuing AML series from 8/31/24
1/ Overview of salvage therapies for relapse refractory AML
#hemonctrainees
#MedTwitter
#hemoncfellows
#weekend_review
#AML
#leusm
Continuing from last review posted on 08/25/24
1/ Overview of consolidation therapy for AML in CR1!
#MedTwitter
#hemonctrainess
#hemtwitter
1
27
102
2
31
107
Venetoclax with decitabine as frontline treatment in younger adults with newly diagnosed ELN adverse-risk AML
1. 93% CRc after C
#2
, 79% MRD neg.
2. median fu 15.3: 12-month OS, EFS, and DOR were 82%, 61%, and 65%, respectively
3. 86% received alloHCT
6
36
102
#weekend_review
#AML
#leusm
Continuing from last review posted on 08/25/24
1/ Overview of consolidation therapy for AML in CR1!
#MedTwitter
#hemonctrainess
#hemtwitter
#weekend_review
#AML
#leusm
1/ Overview of AML induction strategies!
#MedTwitter
#hemoncfellows
#hemonctrainees
2
52
169
1
27
102
Finally out ➡️ A huge shout out for
@MRLitzow
@eaonc
@MayoCancerCare
Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults | New England Journal of Medicine
➡️ consolidation Blina improves OS in MRD-ve Ph-ve B-cell ALL
2
24
101
Weekend review 📖 🧵 1/5
The story of Luspatercept!
Luspatercept, TGF-B fusion trap protein, neutralizes TGF-B and restore effective erythropoiesis.
1
26
96
Super happy with this effort! Re-exploring the efficacy of allo-HCT in TP53m AML. 👇🏽 Extremely grateful to all collaborators of COMMAND consortium!
6
33
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Allogeneic HCT vs Consolidation Chemotherapy in Patients With Intermediate-Risk Acute Myeloid Leukemia via
@JAMAOnc
part of
@JAMANetwork
-> Randomized trial showing no overall survival benefit of alloHCT in int. risk AML, < 60 yrs with available donor!
5
13
87
Upfront immunotherapy +/- chemotherapy for precursor B-cell (BCP) ALL
From Rituximab > Inotuzumab (InO) > Blinatumomab > InO/Blina > “chemo free” induction.
Review of literature in a 🧵
4
27
87
#Weekend_review
🧵
1/7 Choice of frontline TKI for chronic myeloid leukemia in chronic phase (CML-CP)
#CML
#BCR_ABL1
#TKI
#Philadelphia_chromosome
#medtwitter
#hemoncfellows
1
12
85
#Weekend_review
🧵
#IMresident
#hemoncfellows
1/10 JAK2 unmutated or non-PV erythrocytosis or idiopathic erythrocytosis
Not every polycythemia/erythrocytosis is polycythemia vera (PV)!
JAK2 unmutated or non-PV erythrocytosis: hereditary and acquired.
Up to 70% of cases,
1
29
86
Molecular, clinical, and therapeutic determinants of outcome in NPM1-mutated AML
Key takeaways
Adverse risk CG, WT1, DNMT3A, FLT3ITD were associated with high rate of MRD+ by PCR & ⬆️ relapses
In spite of high risk molecular features, MRD- overcome bad
5
20
85
#Weekend_review
#AML
#leusm
1/ Post transplant maintenance for AML
1) How should you define effectiveness?
2) Pts that can benefit the most?
3) What should be the duration of therapy?
Review of literature, pitfalls
7
19
84
2
25
78
#weekend_review
🧵
1/6 Myelofibrosis after failure of Ruxolitinib
JAK inhibitors are incorporated into management for splenomegaly and improved QOL from symptom improvement.
50% of patients discontinue treatment @ 3 years and 75% @ 5 yrs, as per data from COMFORT-I and II
3
18
79
Weekend review 📖
#ASH23
, few selected
#MDS
abstracts to watch out at this year ASH meeting
@ASH_hematology
#mdssm
🧵 👇🏽
3
15
75
Phase 3 trial of gilteritinib plus azacitidine vs azacitidine for newly diagnosed FLT3mut AML ineligible for intensive chemotherapy ⬆️ Higher response rate with combo ⬇️ no improvement in OS. ➡️ AZA, Ven, Gilt triplet given sequentially, may be the answer
6
19
72
Management of Philadelphia chromosome positive acute lymphoblastic leu...
@MKD_BMT
@aljurf100
#ALL
#leusm
1
31
72
Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1 1. DMNT3A mutation in NPMm
#AML
have inf survival outcome. 2. AlloHCT can potentially overcome adverse outcome.
#leusm
#MedTwitter
1
17
69
#EHA2024
#EHA24
#magrolimab
#CD47
Dr Daver
@Daver_Leukemia
: Presented results of ENHANCE-3 study; magrolimab+venetoclax+AZA vs AZA+VEN in newly diagnosed AML.
1) the trial did not show improvement in CR or OS with triplet.
2) Magrolimab combination led to more fatal AEs (grade
3
13
69
Weekend reading 📖
#ASH23
, few selected
#ALL
abstracts to watch for at this year ASH
@ASH_hematology
#leusm
🧵 👇🏽
3
13
66
Weekend review
Outcome of relapsed APL
1/7 Generally, with ATO+ATRA induction CR ⬆️ 90%, long-term OS 70-80%
Relapses are less common, prior ATO may led to resistance(Zhu NEJM 2014), no clear consensus on auto vs allo-HCT
Brief 🧵salvage therapy for relapse APL and outcome
2
14
65
Outcome of pts with persistence MRD in NPM1m AML (n= 100)
👉🏾42% progression free at 1 yr:
(1)30% Spontaneous CR with MRD -ve
(2) 12% low level MRD
👉🏾 relapse assoc. with:
(1)FLT3m
(2)NPM MRD at end of treatment.
#leusm
#AML
@AML_Hub
@BloodAdvances
3
22
65
After 2 weeks of inpatient service, time to play
#weekend_cricket
to energize and continue to do which I love, take care of leukemia patients with compassion!
9
0
67
Weekend review 📖
1/8. Brief review of menin inhibitors in clinical trials 🧵
KMT2Ar AL characterized by aberrant overexpression of HOX genes
menin is necessary for KMT2A to bind HOX gene for leukemogenesis
Similarly with NPM1 and NUP98-rearranged.
3
13
64
1/8 Weekend review 📖
Sub-group of AML with targetable mutation have sub-optimal response ➡️VEN + HMA e.g FLT3m, KMT2A
OR
sequencing targeted therapy post VEN have modest responses e.g IDH1/2i
Brief review focusing on VEN+HMA triplets in AML 🧵
#leusm
#VEN_HMA_triplets
3
12
65
Thrilled to present today regarding outcome of TP53m AML in the era of novel therapies.
@MRLitzow
@yasminabaza1
@Anand_88_Patel
@Dr_RoryShallis
and on behalf of colleagues not on twitter.
#leusm
#ASH21
3
7
66
Early View | Haematologica Clinical and molecular correlates of somatic and germline DDX41 variants in pts & families with myeloid neoplasms: super proud of this effort highlighting the challenges of variant interrogations in DDX41m myeloid neoplasm.
3
17
65
Weekend review 📖
1/7 🧵
➡️ Outcome of patients progressing after venetoclax based therapies
➡️ Mechanism of venetoclax resistance
➡️ Possible strategies to overcome resistance 👇🏽
#leusm
6
18
65
#weekend_review
#MDS
#mdssm
🧵
Rx of Lower risk MDS, non del 5q, failing ESA/luspatercept
Huge unmet medical need!!
#ASH
-image of MDS-RS 👇🏽
3
8
62
Weekend reading 📖
Upfront therapy for FLT3 mutated AML.
Brief overview on FLT3i evaluated in phase 2 and phase 3 studies👇🏽
2
18
61
Congratulations to
@TalhaBadarMD
on his masterful oral presentation of data generated from our COMMAND consortium re TP53-mutated AML and differential outcomes between HMA- vs HMA-VEN-treated patients
@yasminabaza1
@Anand_88_Patel
@MRLitzow
3
11
43
2
2
61
American Journal of Hematology | Blood Research Journal | Wiley Online Library
➡️ Outcome after stopping VEN+AZA:
28/62 ND AML pts stopped HMA+VEN
With a median follow-up of 23 months (IQR, 20–32), mOS and treatment-free survival were 44 (IQR, 16-NR)
2
10
59
Weekend review 📖
~ 50% of pts with myelofibrosis discontinue ruxolitinib after 3 yrs: d/t progression/suboptimal response/cytopenia
Outcome after ruxolitinib is poor: mOS ~ 14 mo
Some novel drugs and combinations with Ruxolitinib that will be presented at
#ASH23
🧵
1
11
57
American Journal of Hematology | Blood Research Journal | Wiley Online Library
Hot from the press
Led by
@n_gangat
@karraromd
28 days of Ven not better than 21/14 days
14D may be suitable for favorable & 21D for adverse AML
@MayoCancerCare
#leusm
1
11
57
Weekend review
1/9 Clinical significance of RAS mutation in AML
2
8
58
Dasatinib/prednisone induction followed by blinatumomab/dasatinib in Ph acute lymphoblastic leukemia At a median follow up of 2.7 years, 3-yr OS and DFS were 87% & 77% respectively. Albeit, shorter f/u these results are encouraging in elderly Ph+ ALL pts
2
11
55
#weekend_review
🧵
Deep dive into ASC4FIRST trial
#CML
Asciminib in Newly Diagnosed Chronic Myeloid Leukemia | New England Journal of Medicine
2
12
56
International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults ➡️ BRAFm found in 50% cases➡️ Rx varies based on organ involved (local to systemic) and BRAFm.
2
16
53
It was a pleasure to present at
@uscnorris
grand rounds regarding
#TP53m
#AML
. Certainly an area of unmet need! Thank you
@abdullahladha
for the invite!
4
8
54
1
21
55
👉🏾 Clonal neutropenia with CHIP inc. risk for hem malignancies.
0
21
52
Azacitidine plus venetoclax in pts with high-risk
#MDS
or
#CMML
: phase 1 results of a single-centre, dose-escalation, dose-expansion, phase 1–2 study ➡️ recommended dose AZA for 5 days and Ven for 14 days. ORR 87%, AE’s cytopenia and PNA
@MDAndersonNews
2
8
51
Weekend reading 📖
Immune based therapies for AML 🧵 1/11
Immune suppression and senescence is one of the features of AML.
Types of immune therapies explored in AML
Bispecific Abs
Check point inhibitors
CAR T
mAbs
Antibody drug conjugates
2
12
52
Haploidentical vs matched unrelated donors for patients with ALL: donor age matters more than donor type 👉younger haplo < 35 yrs had better OS (in spite of high % of adverse CG) , less NRM, less GVHD than older MUD.
#leusm
#MedTwitter
0
16
48
FDA grants accelerated approval to ponatinib with chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia
Based on positive data with improvements in MRD-ve CR with ponatinib compared to imatinib with low intensity chemo!
#Ph_pos_ALL
2
16
50
So refreshing to meet the one and only Dr. Qazilbash
@Transplant_Doc
Who has mentored many, including me!
#ASH23
1
0
52
Outcomes of TP53m AML with evolving frontline therapies: Impact of alloHCT on survival. Finally published! ➡️Interestingly Rx evolved with time CPX-351➡️HMA+Ven: inc CR rates (OR 3.0), no improv. in OS. AlloHCT retained OS benefit in MVA.
3
13
49
#EHA2024
#EHA24
#myelofibrosis
#mpnsm
Koschmieder: current standard and novel targets for myelofibrosis in 2024!
2
12
51
20-Year Steady Increase in Survival of Adult Patients with Relapsed Philadelphia-Positive Acute Lymphoblastic Leukemia Post Allogeneic Hematopoietic Cell Transplantation 2 yrs post alloHCT relapse improve from 27.8% to 54%.
#leusm
@Mohty_EBMT
et al.
2
9
47
Always enjoy company of Dr. Patnaik
@MrinalPatnaik
! Great mentor!! I am grateful 🙏🏾 for his guidance and support.
#ASH22
1
0
49
Review on RR T-cell ALL
1/9 T cell ALL comprised 12-15% of ALL, unlike B-cell effective Rx are lacking esp. for RR disease
Relapsed Refractory T cell ALL have poor outcome with mOS 6-9 mo
Novel therapies explored to improve outcome 👇🏽 🧵
#leusm
1
11
47
Early View | Haematologica Allo-HCT conditioning regimen and outcome in myelofibrosis
@CIBMTR
analysis. ⬇️ In multivariable analysis with RIC, Fludarabine/melphalan was associated with inferior OS (HR 1.80, 95% CI 1.15-2.81, p=0.009), higher early NRM (HR
1
18
49
ASH 2023 Summary: "The Best of Acute Leukemia and MDS - Highlights & Key Takeaways" | VuMedi via
@vumedi
0
13
49
Outcomes of allogeneic transplant in pts with DDX41m
#MDS
&
#AML
Kudos to
#Dr_Anmol_Baranwal
#Dr_Alkhateeb
@AlkaliDr
@MrinalPatnaik
1st report on outcome - DDX41m MDS/AML receiving alloHCT. We may have to Rx as favor. risk disease with alloHCT for relapse!
3
8
49
Clinical outcome of myelodysplastic syndrome progressing on hypomethylating agents with evolving frontline therapies: continued challenges and unmet needs
@BloodCancerJnl
Happy to share our paper, thanks to
@AhmadGhorab
for working on it.
@MayoCancerCare
1
12
48
Dasatinib plus dexa —> AlloHCT.
CR 98.5%, CMR 40%. 5-year DFS 37%, OS 48%.
Causes of relapse. 1) T315Im 2) p210 BCR-ABL1 isoform 3) isolated CNS relapse.
0
16
48
#EHA2024
#EHA24
#menin_inhibitors
1/3 Kuhn: summarizes menin inhibitors in clinical 🧵
1) In preclinical models showed synergy with FLT3i and BCL2i
2) menin inhibitors showing excellent response rates with Ven+HMA
3) Ziftomenib received breakthrough designation and
2
11
48
Long-Term Results of the Dasatinib-Blinatumomab Protocol for Adult Philadelphia-Positive ALL
With median fu of 53 mo DFS and OS are 75.8% and 80.7%!
IKZF1 plus and emergence of T315I suggestive of inferior outcome.
#ALL
#leusm
#Phpos_ALL
2
13
47
Weekend reading 📖
Tweetorial 🧵
1/9
Moving immunotherapy upfront in B-cell ALL
Due to increase understanding of disease biology, resistance/toxicity from chemotherapy, field is moving towards early introduction of targeted molecule and immunotherapy.
1
11
47
Weekend reading 📖
#ASH2023
abstracts are out, few selected
#AML
abstracts to watch for at this year ASH
@ASH_hematology
#leusm
🧵 👇🏽
4
9
46
#EHA2024
#EHA24
#IDHinhibitors
Therapeutic targets in AML
Botton: IDH inhibitors in AML
1) R172 sub-group has excellent outcome
2) sub-optimal responses with IDHi are mainly due number of concurrent somatic mutations (slide 2)
3) triplet combinations showed 100% responses
0
9
47
#ASH23
mandatory 🤳 😂 from the airport: destination 🛫
#SanDiego
Very excited to meet colleagues and friends. Make new collaborations, boost existing ones!
@ASH_hematology
1
1
47
Daunorubicin-60 versus daunorubicin-90 versus idarubicin-12 for induction chemotherapy in acute myeloid leukemia: a retrospective analysis of the Mayo Clinic experience | Haematologica
@AlkaliDr
@MrinalPatnaik
@MayoCancerCare
2
12
46
Weekend review
1/11 Outcome of MDS progressing on hypomethylating agent has dismal OS in the range of 6-9 months; worse with
#TP53m
No approved therapy for this poor prognostic disease.
👇🏽 🧵 on prospective and retrospective studies.
4
9
44
Hypomethylating Agent Monotherapy Compared With Hypomethylating Agent Plus Venetoclax Regimen Among Patients With Untreated TP53-Mutated AML
0
5
46
1/9 Weekend review
#Menin_inhibitors
#leusm
#MLL
#KMT2A
MLL- rearrange acute leukemia (AL).
Recently there has been lot of interest in the management of MLL-rearranged acute leukemia, courtesy development of novel Menin inhibitors.
Brief overview on MLL gene re-arranged AL in
3
10
44
Prospect of CAR T-cell therapy in acute myeloid leukemia
@MKD_BMT
#DrHongQin
@MayoCancerCare
#leusm
#CARTcell
1
17
45