Received: 14 June 2023 Revised: 1 August 2023 Accepted: 9 August 2023

DOI: 10.1002/ajh.27063

CORRESPONDENCE

Teclistamab in patients with multiple myeloma and impaired

renal function

To the Editor:
B-cell maturation antigen (BCMA) expressed in B-cells, normal
plasma cells and multiple myeloma (MM) cells has emerged as a
novel target for therapy in relapsed or refractory multiple myeloma
(RRMM). The United States Federal Drug Administration (FDA)-
approved BCMA targeting therapies now include teclistamab,1 cilta-
cabtagene autoleucel, and idecabtagene vicleucel. Teclistamab is a
T-cell directing bispecific antibody with FDA approval for patients
who have received at least 4 lines of previous therapy, including
a proteasome inhibitor (PI), an immunomodulatory (IMiD) agent,
and an anti-CD38 monoclonal antibody. The European Medicines
Agency (EMA) approval for teclistamab allows for use in patients
who have received at least three prior lines of therapy including a
PI, IMiD agent, and an anti-CD38 monoclonal antibody. In the piv-
otal MajesTEC-1 trial, teclistamab led to high overall response rate
(ORR) of 63%, 39% of those achieving a complete response (CR) or
better, low incidence of severe cytokine release syndrome (CRS),
but high risk of infections.1
MajesTEC-1 excluded patients with an estimated glomerular fil-
tration rate (eGFR) <40 mL/min, and in fact 73% of patients had eGFR
>60 mL/min. Therefore, there is no clinical trial evidence for the
safety and efficacy of teclistamab in patients with severely impaired
renal function, a circumstance common at this point in their disease
trajectory.2 With the commercial availability of teclistamab, its use
is expected in patient populations not necessarily reflected in
MajesTEC-1. We aim to report our preliminary experience on the
safety and outcomes of patients with severely impaired renal function
treated with teclistamab.
We have treated seven consecutive patients with severely
impaired renal function, including four with end stage renal disease
(ESRD) on renal replacement therapy at the time of initiation of teclis-
tamab (Table 1). These patients did not have any available treatment

TABLE 1 Characteristics of seven consecutive patients with RRMM and severe renal impairment treated with teclistamab.

Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7

Age 60 60 74 73 67 47 48
Sex F M M F F F M
ECOG performance status 2 2 2 2 2 2 3
Months since diagnosis 79 203 25 46 81 156 15
MM isotype IgGκ IgGκ IgGλ IgAκ IgGλ IgAλ IgAκ
Cytogenetic abnormalities +1q, t(11;14) N/A +1q del(13) N/A hypodiploid +1q, del(13),
hyperdiploid
Extramedullary plasmacytoma No No No No Yes No Yes
No. of prior lines of therapy 6 4 4 4 7 5 4
Triple-class refractory Yes Yes Yes Yes Yes Yes Yes
Penta-drug refractory Yes No Yes No Yes Yes Yes
Prior AHCT Yes Yes No Yes Yes No No
Prior BCMA-directed CAR-T CAR-T No No No No No No
eGFR at time of Teclistamab initiation (ml/min) HD HD HD 16 22 27 HD
Maximum CRS Grade 1 1 2 1 3 1 0
ICANs No No No No No No No
Infections None None None None None None None
Duration of follow-up (months) 7 2 2 5.5 1.5 4 1
Best response VGPR VGPR VGPR VGPR PD VGPR PD

Abbreviations: AHCT, autologous hematopoietic cell transplantation; BCMA, B-cell maturation antigen; CAR-T, chimeric antigen receptor t cell; CRS,
cytokine release syndrome; eGFR, estimated glomerular filtration rate; HD, hemodialysis; ICANS, immune effector cell-associate neurotoxicity syndrome;
PD, progression of disease; PR, partial response; VGPR, very good partial response.

Am J Hematol. 2023;1–3. wileyonlinelibrary.com/journal/ajh © 2023 Wiley Periodicals LLC. 1


2 CORRESPONDENCE
option with demonstrated safety in individuals with severe renal
impairment. The patients were considered ineligible for all available
clinical trials at the institution, primarily driven by their renal function.
None of the seven patients would have met inclusion criteria for
MajesTEC-1 due to poor renal function and performance status.
Additionally, two would not have met criteria based on platelet count,
one based on hemoglobin concentration, and one based on prior
BCMA-directed therapy (3 years prior to teclistamab). Five of the
patients had longstanding renal impairment. Two patients (patients
6 and 7) had rapidly worsening renal function related to myeloma
progression. All the patients previously provided written informed
consent to be included in institutional myeloma database.
According to prescribing information, teclistamab pharmacokinetics
were not significantly impacted by mild or moderate renal impairment.3
It stands to reason, based on the general principals of monoclonal anti-
body elimination (excretion and catabolism) and pharmacokinetics
reported for teclistamab, that patients with severe renal impairment
including those with ESRD on hemodialysis should also be able to
4
receive teclistamab without significant change on pharmacokinetics.
Risk evaluation and mitigation strategy (REMS) requirements
were satisfied, and all the patients were hospitalized for observation
according to prescribing information for doses within the step-up
phase. We followed the dosing and frequency recommendations
listed in the FDA-approved prescribing information and did not
10968652, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ajh.27063 by Duodecim Medical Publications Ltd, Wiley Online Library on [24/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
employ any modifications for cycles 1 and 2. For patients on hemodi-
alysis, if dosing was anticipated on a dialysis day, arrangements were
made for the dose to be administered after hemodialysis. Once
patients were transitioned to the outpatient setting, target doses were
given on a non-dialysis day. At cycle 3, dose frequency was modified
for every 2 weeks for 8 doses, then every 4 weeks from cycle
7 onward. Infection mitigation included oral levofloxacin, prophylaxis
for Herpes simplex virus/varicella zoster virus, and Pneumocystis
jirovecii starting at onset of teclistamab therapy. We administered
monthly intravenous immunoglobulin (IVIG) starting on the second
month.5
Median follow-up from onset of teclistamab therapy is 2 months
(range 1–7). Preliminary anti-myeloma activity is indicated in Figure 1.
Among the seven patients reported, five demonstrated treatment
response without indication of increased toxicity and they continued
teclistamab treatment to date with evidence of very good partial
response (VGPR). Two patients (patients 5 and 7) demonstrated dis-
ease progression on teclistamab and discontinued treatment prior to
second cycle. It is interesting to note that extramedullary plasmacyto-
mas were present in both patients. This observation is aligned with
the lower likelihood of response to teclistamab in patients
with EMD.1 CRS occurrence and grading in these patients follows
established data for teclistamab. While patient 5 did experience grade
3 CRS, due to our small sample size, it should be noted that the
F I G U R E 1 Trajectory of
affected free light chain in seven
consecutive patients with severe
renal impairment treated with
teclistamab. Affected light chain is
displayed given its short half-life
enabling early assessment of anti-
myeloma activity.

CORRESPONDENCE
incidence of 14% may not be representative of the population at
large. No immune effector cell-associated neurotoxicity syndrome
(ICANS) or infections have been reported in these patients to date.
One patient (patient 6) with acute renal impairment related to mye-
loma progression had substantial renal improvement (eGFR from
27 mL/min to 56 mL/min after 1 cycle). Patient 4 had stable renal func-
tion and patient 5 experienced worsening renal function along with dis-
ease progression.
Up to 50% of patients may have impaired renal function at
diagnosis of MM, and despite treatment, an estimated 25%–50% of
6
patients will develop new or worsening renal impairment. While
not yet prospectively studied in this population, teclistamab therapy
should be considered in patients with eGFR <40 mL/min, including
those with ESRD. Even as our initial experience reported here is
limited by short follow-up time and a small sample size, safety and
responses appear to be comparable to overall population reported
in MajesTEC-1. Future studies are warranted to study safety and
efficacy of teclistamab in populations not represented in clinical
trials.
CONF LICT OF IN TE RE ST ST AT E MENT
Luciano J. Costa received research funding from BMS, Janssen,
AbbVie, Amgen, Genentech; honorarium from BMS, Janssen, Amgen,
Pfizer, Adaptive biotechnologies. Susan Bal received honorarium from
AbbVie, Adaptive Biotechnologies, Bristol Myers Squibb, Janssen, and
MJH Lifesciences. The remaining authors have no relevant conflicts of
interest to disclose.
DATA AVAI LAB ILITY S TATEMENT
The data that support the findings of this study are available from the
corresponding author upon reasonable request.
10968652, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ajh.27063 by Duodecim Medical Publications Ltd, Wiley Online Library on [24/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
3
Laura Joiner 1, Susan Bal 2, Kelly N. Godby 2, Luciano J. Costa 2
1
Department of Pharmacy, University of Alabama at Birmingham,
Birmingham, Alabama, USA
2
Division of Hematology and Oncology, University of Alabama at
Birmingham, Birmingham, Alabama, USA
Correspondence
Luciano J. Costa, Division of Hematology and Oncology, Department
of Medicine, University of Alabama at Birmingham, 1802 6th Avenue
South, Birmingham, AL 35294, USA.
Email: ljcosta@uabmc.edu
OR CID
Luciano J. Costa https://orcid.org/0000-0001-5362-2469
RE FE RE NCE S
1. Moreau P, Garfall AL, van de Donk N, et al. Teclistamab in relapsed or
refractory multiple myeloma. N Engl J Med. 2022;387(6):495-505.
2. Dimopoulos MA, Sonneveld P, Leung N, et al. International myeloma
working group recommendations for the diagnosis and Management of
Myeloma-Related Renal Impairment. J Clin Oncol. 2016;34(13):1544-1557.
3. TECVAYLI (teclistamab-cqyv) injection. Prescribing information. 2022
https://www.janssenlabels.com/package-insert/product-monograph/
prescribing-information/TECVAYLI-pi.pdf 2023.
4. Ryman JT, Meibohm B. Pharmacokinetics of monoclonal antibodies.
CPT Pharmacomet Syst Pharmacol. 2017;6(9):576-588.
5. Mohan M, Chakraborty R, Bal S, et al. Recommendations on prevention
of infections during chimeric antigen receptor T-cell and bispecific anti-
body therapy in multiple myeloma. Br J Haematol. 2023. doi:10.1111/
bjh.18909
6. Dimopoulos MA, Mikhael J, Terpos E, et al. An overview of treatment
options for patients with relapsed/refractory multiple myeloma and
renal impairment. Ther Adv Hematol. 2022;13:20406207221088458.