You've Got the MIDAS touch
The MIDAS Consortium consists of 3 academic institutions that reported consecutive patients. Name the centers & the number of patients reported.
What is: Ohio State University, Moffitt Cancer Center, & Roswell Park
*239 consecutive patients
The global expanded access program (EAP) study contained 2 defined age categories, with a total number of ___ patients.
What is:
1. Children-- < 16 y.o.
2. Adults-- >/= 16 y.o.
**136 patients
""How do we know if Yartemlea is working?
What is....
Clinical judgment along with serial monitoring of harmonized TA-TMA clinical & laboratory paramenters over time.
In clinical studies, response was: improvement or stabilization of TMA markers & organ dysfunction OR independence from transfusion.
Why would a clinician consider utilizing the Harmonization criteria to identify TMA .
What is.....the Harmonization criteria, created by 19 adult & pediatric transplanters from US, Asia, & Europe representing major transplant groups across the world, "harmonized" 6 different tools into one clear & comprehensive tool.
For patients who are underinsured, uninsured, or need co-pay assistance, the office staff or patient representative may call this program.
*For an extra 100 pts (daily double), what is the phone number.
YARTEMLEAssist
1-844-YARTEM1 (1-844-927-8361, option 2)
The incidence of TMA was scored using 6 published criteria, the center-reported diagnosis, & 3 MIDAS adjudication categories.... name those categories.
What is: None, Non-severe, & Severe
Although YARTEMLEA dosing was similar to the (Khaled) pivotal trial, frequency was different.
What is: Administer IV TWICE weekly initially for at least 8 weeks.
Change in frequency was allowed based on the treating physician's assessment of treatment response.
When a patient exhibits early renal changes post-transplant, I do not usually suspect TMA. Instead, I consider a more broad differential.
What is: Doctor...Renal dysfunction is common after HCT & may result from medication toxicity, infection, BP fluctuations, or GVH disease. However, TMA is an important & often underrecognized contributor to transplant -associated renal injury. Early consideration of TA-TMA may support timely diagnosis & appropriate mgmt and help limit progression to severe or irreversible organ damage.
Hi-Risk TMA has been associated with this outcome.
What is .....Non Relapsed Mortality (NRM)
In the Matsui, et al published article: Survival in adults with high-risk TA-TMA, the data for the comparative analyses was obtained from 3 sources.
What is:
1. Pivotal trial (Khaled) single-arm, open-label
2. Narsoplimab EAP trial
3. Kyoto Stem Cell Transplantation Group (KSCTG) registry who were diagnosed with TA- TMA
Name the cumulative incidence of ANY TA-TMA by day +100 after stem-cell transplant, as well as the incidence of severe TMA by day +100 as reported in the MIDAS study.
What is 56.9%, and 21.8%.
In the EAP study, name the safety signals of concern with Narsoplimab treatment.
What is....
NONE
ZERO
ZILCH! :)
If the PI says I can administer YARTEMLEA one to two times weekly, how do I know what is the best frequency to use?
What is....the PI provides flexibility in dosing based on clinical judgement & patient response, it does not mandate a specific sequencing strategy.
*Patients should be monitored over time & dosing frequency based on clinician's evaluation of response & tolerability.
If a patient cannot safely undergo a renal biopsy, TA-TMA can be diagnosed if certain criteria are present.
What is: 4 or more of the following, at least 2 incidences in 2 weeks:
1. Anemia
2. Thrombocytopenia
3. Elevated LDH (>ULN)
4. spot random urine protein/creatinine ratio (rUPCR) >/= 1mg/mg
5. HTN
6. Schistocytes (present)
7. Elevated sC5b-9 (>ULN)
There are 2 specific recommended doses for YARTEMLEA, with frequency variation.
Weight:
>/= 50 kg (110 lbs)--370 mg IV over 30 min once weekly. **May increase to twice weekly if inadequate improvement of TA-TMA S&S
<50 kg (110 lbs)--4mg/kg, IV over 30 min once weekly. **May increase to twice weekly if inadequate improvement of TA-TMA S&S
*If dose is missed, administer dose ASAP
Patient eligibilty for MIDAS consisted of 3 criteria.
What is: >/= 18
undergoing 1st allo-HCT
any indication for their HCT.
Inclusion criteria for EAP enrollment included a diagnosis of TA-TMA defined as.....
****************************
While exclusion criteria included....
What is: Thrombocytopenia & evidence of microangiopathy
*********************************
Malignant hypertension or uncontrolled infection
Your HCP argues that TMA is not an issue at their transplant center because post-transplant cyclophosphamide (PT-CY)is a part of their protocol.
What is.....Doctor, while PT-CY has been associated with educed rates of GVHD and improvements in certain transplant outcomes, current evidence does not support that PT-CY eliminates the risk of TA-TMA. In fact, published data indicates that TA-TMA can still occur and may be severe despite PT-CY based prophylaxis.
According to the article: Harmonizing Definitions for Diagnostic Criteria & Prognostic Assessment of TA-TMA, the summary of consensus key points identifies that TA-TMA can be diagnosed in 3 ways.
What is: renal biopsy
intestinal biopsy
clinically, using the modified Jodele criteria
In the pivotal trial (Khaled, et al, Journal of Clinical Oncology, Aug. 2022), patients met the primary endpoint by showing required clinical improvement in 2 categories.
What is:
1. laboratory TMA markers--platelet count AND LDH
2. organ function OR freedom from transfusion
Key results from the MIDAS study identified early indicators of TA-TMA. What are they...
What is....Day +7--increased serum creatinine
Day +14--HTN
The 1 year OS in ped. & adult patients receiving 1st line Narsoplimab was 75% and 58%, respectively.
What is the 1yr OS for >/= 2nd line of therapy......
BONUS......of the pts receiving 2nd line + therapy, what percentage were refractory to Ecu
What is.....
Peds = 56.2%
Adults = 40.5%
BONUS.....peds-- 84%; adult--100%
In conversation with your HCP, he voices he is completely comfortable with prescribing Eculizumab for his TA-TMA patients.
What is.....
1. Yartemlea is the only FDA therapy specifically approved for the treatment of TA-TMA.
2. With YARTEMLEA's distinct MOA, the lectin pathway of complement is selectively inhibited, while preserving the classical & alternative pathways...this allows the patient's important host immune defense to remain intact.
3. YARTEMLEA does not carry a black boxed warning, no REMS program involved, no meningococcal vaccinations needed, and no need for supplemental dosing following therapeutic plasma exchange.
Certain features are associated with increased non-relapsed mortality (NRM) in patients with TA-TMA & are considered high-risk features. Name 3 of the 6.
What is: sC5b-9 (>ULN)
spot rUPCR (>/= 1 mg/mg)
elevated LDH (>/=2 times ULN)
Gr. II - IV acute GVHD
infections (viral or bacterial)
Any organ dysfunction, except KDIGO acute kidney injury stage I
The benefit of YARTEMLEA treated patients with TA-TMA in reducing mortality risk was analyzed using well-matched external controls in this published paper with survival curves for 4 specific risk factor subgroups.
What is: Blood Adv 2026 Jan 13--Matsui, et al.. Survival in adults with high-risk TA-TMA: a comparative analysis of narsoplimab vs supportive care
Patients with:
*Elevated LDH >/= 2 times ULN
*GVHD
*Organ Dysfunction
*Systemic Infection