Lenalidomide: A double‐edged sword for concomitant multiple myeloma and post‐essential thrombocythemia myelofibrosis

Loscocco, Giuseppe Gaetano; Antonioli, Elisabetta; Romano, Ilaria; Vergoni, Federica; Rotunno, Giada; Mannelli, Francesco; Guglielmelli, Paola; Vannucchi, Alessandro M.

doi:10.1002/ajh.26153

Cited by 4 publications

(4 citation statements)

References 31 publications

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“…There are more reports of asynchronous MM and ET, as summarized in Table 2 [13][14][15][16][17][18][19][20][21][22][23][24]. The median patient age was 67 years, with 9 males and 5 females.…”

Section: Discussion/conclusionmentioning

confidence: 99%

A case of synchronous dual hematological malignancy: effects of multiple myeloma therapy on essential thrombocythemia and vice versa

Krishnan

Price

Kotchetkov

2023

Preprint

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Section: Discussion/conclusionmentioning

confidence: 99%

A case of synchronous dual hematological malignancy: effects of multiple myeloma therapy on essential thrombocythemia and vice versa

Krishnan

Price

Kotchetkov

2023

Preprint

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“…There are more reports of asynchronous MM and ET, as summarized in Table 2 ( 13 – 24 ). The median patient age was 67 years, with nine men and five women.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Effects of multiple myeloma therapy on essential thrombocythemia and vice versa: a case of synchronous dual hematological malignancy

2023

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BackgroundDual hematological malignancies, asynchronous or synchronous, are underrecognized entities and are usually suspected when clinical, hematological, or biochemical features cannot be explained by the primary malignancy alone. We present a case of synchronous dual hematological malignancies (SDHMs), where the patient was diagnosed with symptomatic multiple myeloma (MM) and essential thrombocythemia (ET), when excessive thrombocytosis occurred following initiation of MPV (melphalan–prednisone–bortezomib) antimyeloma therapy.Case descriptionAn 86-year-old woman presented to the emergency in May 2016 with confusion, hypercalcemia, and acute kidney injury. She was diagnosed with free light chain (FLC) lambda and Immunoglobulin G (IgG) lambda MM and started MPV (standard of care at that time) treatment with darbopoietin support. At diagnosis, she had normal platelet count since the ET was likely masked by bone marrow suppression due to active MM. After she reached stringent complete remission with no MP detected on serum protein electrophoresis or immunofixation, we noticed that her platelet counts increased to 1,518,000 × 109/L. She was tested positive for mutation in exon 9 of calreticulin (CALR). We concluded that she had concomitant CALR-positive ET. After bone marrow recovery from MM, the ET became clinically apparent. We started hydroxyurea for ET. Treatment for MM with MPV did not affect the course of ET. Presence of concomitant ET did not decrease the efficacy of sequential antimyeloma therapies in our elderly and frail patient.ConclusionThe possible mechanism underlying the occurrence of SDHMs is unclear but is likely due to stem cell differentiation defects. SDHMs can be challenging to treat and warrant several considerations. In the absence of clear guidelines on how to manage SDHMs, management decisions depend on several factors including disease aggressiveness, age, frailty, and comorbidities.

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“…Four years later, the progression to post‐ET myelofibrosis was documented. After another 2 years, the MGUS evolution to the IgG lambda MM was observed 10 …”

Section: Figurementioning

confidence: 99%

“…The question is that of the medical significance of the presented data. In our opinion, more attention should be paid to the monitoring of MPN patients for the presence of MGUS, to allow for an early diagnosis of MM and the initiation of an appropriate treatment 10 . Still, the study of the genetic aberration profile in MPNPh‐patients with coexisting MM is needed to precisely define and attack common molecular target(s) responsible for oncogenesis 18 …”

Section: Figurementioning

confidence: 99%

HRAS mutation positive multiple myeloma in the type 2 CALR mutation positive essential thrombocythemia: A case report

Lewandowski

Agata

Kanduła

et al. 2023

J Cellular Molecular Medi

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Out of BCR‐ABL negative myeloproliferative neoplasm (MPNPh − ) patients, 3%–14% display a concomitant monoclonal gammopathy of unknown significance (MGUS). In most cases, the diagnosis of plasma cell dyscrasia is either synchronous with that of MPNPh − or occurs later on. We present a 50‐year‐old patient with type 2 CALR Lys385Asnfs*47 mutation positive essential thrombocythemia (ET) who developed symptomatic multiple myeloma (MM) 13 years after the diagnosis of ET during PEG‐INF2α treatment. The NGS study performed at the time of the MM diagnosis revealed the HRAS Val14Gly/c.41T〉G mutation and the wild type CALR , JAK2 and MPL gene sequence. In the presented case, the complete molecular remission of ET was achieved after 16 months of PEG‐INF2α treatment. The origin of MM cells in MPNPh − patients remains unknown. Published data suggests that type 2 CALRins5 up‐regulate the ATF6 chaperone targets in hematopoietic cells and activate the inositol‐requiring enzyme 1α‐X‐box‐binding protein 1 pathway of the unfolded protein response (UPR) system to drive malignancy. It cannot be excluded that endoplasmic reticulum stress induced by the increased ATF6 resulted in an abnormal redox homeostasis and proteostasis, which are factors linked to MM. The presented case history and the proposed mechanism of mutant CALR interaction with UPR and/or ATF6 should initiate the discussion about the possible impact of the mutant CALR protein on the function and genomic stability of different types of myeloid cells, including progenitor cells.

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Lenalidomide: A double‐edged sword for concomitant multiple myeloma and post‐essential thrombocythemia myelofibrosis

Abstract: A physician or a group of physicians considers presentation and evolution of a real clinical case, reacting to clinical information and data (bold face type). This is followed by a discussion/commentary

Cited by 4 publications

References 31 publications

A case of synchronous dual hematological malignancy: effects of multiple myeloma therapy on essential thrombocythemia and vice versa

A case of synchronous dual hematological malignancy: effects of multiple myeloma therapy on essential thrombocythemia and vice versa

Case Report: Effects of multiple myeloma therapy on essential thrombocythemia and vice versa: a case of synchronous dual hematological malignancy

HRAS mutation positive multiple myeloma in the type 2 CALR mutation positive essential thrombocythemia: A case report

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