PMID- 33161453
OWN - NLM
STAT- MEDLINE
DCOM- 20210126
LR  - 20210126
IS  - 1432-0584 (Electronic)
IS  - 0939-5555 (Linking)
VI  - 100
IP  - 2
DP  - 2021 Feb
TI  - Carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple 
      myeloma patients: the real-life experience of Rete Ematologica Pugliese (REP).
PG  - 429-436
LID - 10.1007/s00277-020-04329-3 [doi]
AB  - Carfilzomib, lenalidomide, and dexamethasone (KRd) have been approved for the 
      treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE 
      clinical trial. However, its effectiveness and safety profile in real clinical 
      practice should be further assessed. We retrospectively evaluated 130 consecutive 
      RRMM patients treated with KRd between December 2015 and August 2018, in 9 
      Hematology Departments of Rete Ematologica Pugliese (REP). The overall response 
      rate (ORR) was 79%, with 37% complete response (CR). Treatment with KRd led to an 
      improvement in response regardless of age, refractory disease, and number and 
      type of previous therapies. After a median follow-up of 18 months, median PFS was 
      24 months and 2y-PFS was 54%. PFS was longer in patients achieving a very good 
      partial response (VGPR) with median PFS of 32.4 months. The relapses after prior 
      autologous transplant (ASCT) positively impact median PFS. Several baseline 
      disease characteristics, such as III ISS scoring or elevated LDH, and prior 
      exposure to lenalidomide were found to negatively impact PFS. Primary refractory 
      or relapsed myeloma patients have been treated with KRd as bridge to ASCT with a 
      great benefit. Thirty-four (83%) reached at least a partial response after KRd 
      and 21 (61%) performed ASCT. In transplanted patients, median PFS was not reached 
      and 2y-PFS was 100%. The treatment discontinuation rate due to adverse events 
      (AEs) was 18%, most commonly for lenalidomide (11%). Overall, in 10% of patients, 
      a KRd dose reduction was necessary at least once (2.5% for carfilzomib and 8% for 
      lenalidomide). The most frequent AE was neutropenia (44%) and anemia (41%). 
      Infections occurred in 14% of patients. Cardiovascular events occurred in 11% of 
      patients. Elderly patients have tolerated therapy very well, without additional 
      side effects compared to younger patients, except for cardiac impairment. Our 
      analysis confirmed that KRd is effective in RRMM patients. It is well tolerated 
      and applicable to the majority of patients outside clinical trials. A longer PFS 
      was shown in patients achieving VGPR, in those lenalidomide naive and in patients 
      relapsing after previous ASCT. Previous ASCT should not hamper the option for KRd 
      therapy. Accordingly, KRd should be used as bridge regimen to ASCT with 
      remarkable improvement in response and PFS rates. Further clinical studies are 
      needed.
FAU - Mele, Anna
AU  - Mele A
AUID- ORCID: 0000-0003-1630-2495
AD  - Department of Hematology and Bone Marrow Transplant, Hospital Card. G. Panico, 
      Via San Pio X, 73039, Tricase (LE), Italy. 
      trialematologia@piafondazionepanico.it.
FAU - Prete, Eleonora
AU  - Prete E
AD  - Department of Hematology and Bone Marrow Transplant, Hospital Card. G. Panico, 
      Via San Pio X, 73039, Tricase (LE), Italy.
FAU - De Risi, Clara
AU  - De Risi C
AD  - Department of Hematology and Bone Marrow Transplant, Hospital Card. G. Panico, 
      Via San Pio X, 73039, Tricase (LE), Italy.
FAU - Citiso, Stefania
AU  - Citiso S
AD  - Department of Hematology and Bone Marrow Transplant, Hospital Card. G. Panico, 
      Via San Pio X, 73039, Tricase (LE), Italy.
FAU - Greco, Giuseppina
AU  - Greco G
AD  - Department of Hematology and Bone Marrow Transplant, Hospital Card. G. Panico, 
      Via San Pio X, 73039, Tricase (LE), Italy.
FAU - Falcone, Antonietta Pia
AU  - Falcone AP
AD  - Department of Hematology and Bone Marrow Transplant, IRCCS Casa Sollievo della 
      Sofferenza, San Giovanni Rotondo, Italy.
FAU - Sanpaolo, Grazia
AU  - Sanpaolo G
AD  - Department of Hematology and Bone Marrow Transplant, IRCCS Casa Sollievo della 
      Sofferenza, San Giovanni Rotondo, Italy.
FAU - Mele, Giuseppe
AU  - Mele G
AD  - Department of Hematology, Hospital Perrino, Brindisi, Italy.
FAU - Giannotta, Angela
AU  - Giannotta A
AD  - Department of Hematology, Hospital Perrino, Brindisi, Italy.
FAU - Vergine, Carolina
AU  - Vergine C
AD  - Department of Hematology, Hospital Vito Fazzi, Lecce, Italy.
FAU - Reddiconto, Giovanni
AU  - Reddiconto G
AD  - Department of Hematology, Hospital Vito Fazzi, Lecce, Italy.
FAU - Palazzo, Giulia
AU  - Palazzo G
AD  - Department of Hematology and Bone Marrow Transplant, Hospital G.Moscati, Taranto, 
      Italy.
FAU - Sabatelli, Sabrina
AU  - Sabatelli S
AD  - Department of Hematology and Bone Marrow Transplant, Hospital G.Moscati, Taranto, 
      Italy.
FAU - Germano, Candida
AU  - Germano C
AD  - Department of Hematology, ASL BT, Barletta, Italy.
FAU - Miccolis, Rosanna
AU  - Miccolis R
AD  - Department of Hematology, ASL BT, Barletta, Italy.
FAU - Curci, Paola
AU  - Curci P
AD  - Department of Hematology and Bone Marrow Transplant, Policlinico, University of 
      Bari, Bari, Italy.
FAU - Palumbo, Gaetano
AU  - Palumbo G
AD  - Department of Hematology, Hospital University Riuniti, Foggia, Italy.
FAU - Offidani, Massimo
AU  - Offidani M
AD  - Department of Hematology and Bone Marrow Transplant, Osp Riuniti Ancona, 
      University of Ancona, Ancona, Italy.
FAU - Rizzi, Rita
AU  - Rizzi R
AD  - Department of Hematology and Bone Marrow Transplant, Policlinico, University of 
      Bari, Bari, Italy.
FAU - Cascavilla, Nicola
AU  - Cascavilla N
AD  - Department of Hematology and Bone Marrow Transplant, IRCCS Casa Sollievo della 
      Sofferenza, San Giovanni Rotondo, Italy.
FAU - Pastore, Domenico
AU  - Pastore D
AD  - Department of Hematology, Hospital Perrino, Brindisi, Italy.
FAU - Di Renzo, Nicola
AU  - Di Renzo N
AD  - Department of Hematology, Hospital Vito Fazzi, Lecce, Italy.
FAU - Mazza, Patrizio
AU  - Mazza P
AD  - Department of Hematology and Bone Marrow Transplant, Hospital G.Moscati, Taranto, 
      Italy.
FAU - Tarantini, Giuseppe
AU  - Tarantini G
AD  - Department of Hematology, ASL BT, Barletta, Italy.
FAU - Guarini, Attilio
AU  - Guarini A
AD  - Department of Hematology, Hospital IRCCS Oncologico, Bari, Italy.
FAU - Capalbo, Silvana
AU  - Capalbo S
AD  - Department of Hematology, Hospital University Riuniti, Foggia, Italy.
FAU - Specchia, Giorgina
AU  - Specchia G
AD  - Department of Hematology and Bone Marrow Transplant, Policlinico, University of 
      Bari, Bari, Italy.
FAU - Greco, Antonino
AU  - Greco A
AD  - Department of Hematology and Bone Marrow Transplant, Hospital Card. G. Panico, 
      Via San Pio X, 73039, Tricase (LE), Italy.
FAU - De Francesco, Rosa
AU  - De Francesco R
AD  - Department of Hematology and Bone Marrow Transplant, Hospital Card. G. Panico, 
      Via San Pio X, 73039, Tricase (LE), Italy.
FAU - Sibilla, Silvia
AU  - Sibilla S
AD  - Department of Hematology and Bone Marrow Transplant, Hospital Card. G. Panico, 
      Via San Pio X, 73039, Tricase (LE), Italy.
FAU - Tonialini, Lorenzo
AU  - Tonialini L
AD  - Department of Hematology and Bone Marrow Transplant, Hospital Card. G. Panico, 
      Via San Pio X, 73039, Tricase (LE), Italy.
FAU - Morciano, Maria Rosaria
AU  - Morciano MR
AD  - Department of Hematology and Bone Marrow Transplant, Hospital Card. G. Panico, 
      Via San Pio X, 73039, Tricase (LE), Italy.
FAU - Pavone, Vincenzo
AU  - Pavone V
AD  - Department of Hematology and Bone Marrow Transplant, Hospital Card. G. Panico, 
      Via San Pio X, 73039, Tricase (LE), Italy.
LA  - eng
PT  - Journal Article
DEP - 20201107
PL  - Germany
TA  - Ann Hematol
JT  - Annals of hematology
JID - 9107334
RN  - 0 (Oligopeptides)
RN  - 72X6E3J5AR (carfilzomib)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - F0P408N6V4 (Lenalidomide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Dexamethasone/administration & dosage/adverse effects
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Lenalidomide/administration & dosage/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy/*mortality
MH  - Oligopeptides/administration & dosage/adverse effects
MH  - Recurrence
MH  - Survival Rate
OTO - NOTNLM
OT  - Autologous transplant and carfilzomib
OT  - Carfilzomib plus lenalidomide and dexamethasone (KRd)
OT  - KRd as bridge therapy
OT  - Real-life experience
OT  - Relapsed/refractory multiple myeloma
EDAT- 2020/11/09 06:00
MHDA- 2021/01/27 06:00
CRDT- 2020/11/08 20:37
PHST- 2020/01/21 00:00 [received]
PHST- 2020/10/27 00:00 [accepted]
PHST- 2020/11/09 06:00 [pubmed]
PHST- 2021/01/27 06:00 [medline]
PHST- 2020/11/08 20:37 [entrez]
AID - 10.1007/s00277-020-04329-3 [pii]
AID - 10.1007/s00277-020-04329-3 [doi]
PST - ppublish
SO  - Ann Hematol. 2021 Feb;100(2):429-436. doi: 10.1007/s00277-020-04329-3. Epub 2020 
      Nov 7.